Direct Segment Aperture and Weight Optimization for Intensity-Modulated Radiotherapy of Prostate Cancer

BACKGROUND AND PURPOSE: To describe the implementation and to evaluate the results of direct segment aperture optimization using the segment outline and weight adapting tool (SOWAT) in intensity-modulated radiotherapy (IMRT) for prostate cancer. PATIENTS AND METHODS: 14 consecutive, unselected patients with localized prostate cancer were entered in a planning study comparing IMRT without and with the use of SOWAT. The clinical target volume (CTV) consisted of the prostate and seminal vesicles in all cases. To create the planning target volume (PTV), a three-dimensional anisotropic margin (10 mm in craniocaudal direction, 7 mm in both other directions) was used. To compare both plans, physical as well as biological endpoints were considered. RESULTS: Considering the CTV, SOWAT resulted in a significantly higher minimal dose together with a higher dose to 95% (D(95)) and 90% (D(90)) of the CTV volume (p < 0.05; Figure 2). Target dose homogeneity was significantly improved (p < 0.001). Tumor control probability (TCP) was significantly increased (p < 0.05). Considering the PTV, D(90) was significantly increased (p < 0.05). Target dose homogeneity was significantly improved (p < 0.05; Figure 1). For rectum, the volumes receiving 50 Gy (R(vol50)), 60 Gy (R(vol60)), or 65 Gy (R(vol65)) as well as the mean dose were significantly lowered after SOWAT (p = 0.0001; Figure 3). Rectal normal tissue complication probability (NTCP) was significantly lower after SOWAT (p = 0.005). Probability of uncomplicated local control (P+) was significantly higher after SOWAT (p < 0.0001). CONCLUSION: SOWAT is a powerful planning tool to increase the therapeutic ratio of IMRT for prostate cancer. It leaves the delivery time unchanged, so that treatments can still be delivered within a time slot of 8 min.     

Long-Term Results in Three-Dimensional Conformal Radiotherapy of Localized Prostate Cancer at Moderate Dose (66 Gy)

PURPOSE: Biochemical control (bNED), disease-specific survival (DSS), overall survival (OS), and late gastrointestinal (GI) and urogenital (UG) side effects (EORTC/RTOG) of patients with long-term follow-up were evaluated. PATIENTS AND METHODS: Three-dimensional radiotherapy up to 66 Gy with/without additional hormonal therapy was performed in 154 prostate cancer (T1-3 N0 M0) patients. According to T-stage, pretreatment prostate-specific antigen (PSA) and grading, patients were divided into a low-, intermediate-, and high-risk group. The 5-, 8-, and 10-year actuarial rates of bNED, DSS and OS and late side effects were calculated. RESULTS: Median follow-up was 80 months. Additional hormonal therapy was given in 57% of patients. Distribution concerning risk groups (low, intermediate, high) showed 15%, 49%, and 36% of patients, respectively. bNED 5-, 8-, and 10-year actuarial rates were 46%, 44%, and 44%. DSS 5-, 8- and 10-year rates amounted to 96%, 90%, and 82%. OS 5-, 8- and 10-year rates were 81%, 64%, and 56%. In uni- and multivariate analysis, only pretreatment PSA (<10 vs. >or=10 ng/ml; p<0.05) and PSA nadir (<0.5 vs. >or=0.5 ng/ml; p<0.0001) affected bNED significantly. Age, risk group, T-stage, grading, and hormonal therapy had no significant influence on bNED, DSS, and OS. Rates of late GI and UG side effects grade>or=2 at 5 years were 17% and 15%. CONCLUSION: Current dose escalation studies with better bNED rates may be able to further increase long-term clinical outcome.     

Radiotherapy of Prostate Cancer with Multileaf Collimators (MLCs)

Background and Purpose: A technical modification for radiotherapy of prostate cancer is presented to smooth the scalloped dose pattern that occurs at treatment field edge, when a multileaf collimator (MLC) has been used. Material and Methods: Ten patients with prostate cancer receiving postoperative, adjuvant irradiation were studied prospectively. By a three-dimensional planning system (TMS, Helax 6.1B) the irradiation was planned for an 18-MV linear accelerator (Primus 1, Siemens). The volumes of interest (VOI) were the planning target volume (PTV; the region of the prostate including the seminal vesicles), the volume of rectum (V_rectum) and urinary bladder (V_bladder). Two four-field techniques (0°, 90°, 180°, 270°) were planned using beams eye view for setting the leaf position of the MLC. For technique A the MLC was adapted to the PTV using a 0° collimator angle for the lateral fields. For technique B the collimator angle of the lateral fields was optimized to compensate the cascade field shape. Dose-volume histograms of PTV, V_rectum and V_bladder were analyzed. The dose was prescribed for the reference point according to ICRU 50. Film dosimetry was used to show the dose pattern at the field edge produced by the two techniques. Results: Dose to PTV did not differ between technique A and B. Median dose to V_rectum was 82.6% for technique A and 77.3% for technique B (p < 0.001). Technique A irradiates a larger V_rectum than technique B being significant for all isodose levels tested. Median dose to V_bladder did not differ for technique A and B (p > 0.05). Conclusion: The presented technical modification is an effective method to blur the staggered dose distribution that results, when the MLC is conventionally stepped to adapt to the dorsal, irregular PTV border in irradiation of prostate. Especially for irradiation to escalated dose levels, this modification may reduce the dose to the rectum and thus the rectal side effects in comparison to the conventional MLC fields.     

Local High-Dose Radiotherapy and Sparing of Normal Tissue Using Intensity-Modulated Radiotherapy (IMRT) for Mucosal Melanoma of the Nasal Cavity and Paranasal Sinuses

PURPOSE: To evaluate the clinical outcome of intensity-modulated radiotherapy (IMRT) in patients with mucosal melanoma (MM) of the nasal cavity and paranasal sinuses. PATIENTS AND METHODS: Between January 1999 and September 2004, eight patients with histologically proven MM of the nasal cavity and paranasal sinuses were treated with IMRT. A median dose of 66 Gy was applied to the macroscopic tumor (gross tumor volume [GTV]; range, 60-68 Gy) as an integrated boost and a median dose of 59 Gy (range, 54-64 Gy) to the clinical target volume (CTV) with IMRT. RESULTS: Treatment-related toxicity was very mild in most patients. Overall survival was 80% at 5 years. Calculated from treatment with IMRT as primary radiotherapy, survival was 100% at 1 year and 75% at 3 years. After IMRT, local progression-free survival was 71.4% at 1 year and 57.1% at 3 years, respectively. Distant progression-free survival after IMRT was 57.1% at 1 year and 28.6% at 3 years. CONCLUSION: Local dose escalation with IMRT yields good treatment results with respect to local and distant tumor control as well as survival, while treatment-related toxicity can be minimized.     

Postoperative Radiotherapy for Prostate Cancer

PURPOSE: To determine the extent of target motion in postprostatectomy radiotherapy (RT) and the value of intensity-modulated radiotherapy (IMRT) compared to three-dimensional conformal radiotherapy (3D-CRT). PATIENTS AND METHODS: 20 patients underwent CT scans in supine position with both a full bladder (FB) and an empty bladder (EB) before RT and at three dates during the RT series. Displacements of the CTV (clinical target volume) center of mass and the posterior border were determined. 3D-CRT and IMRT treatment plans were compared regarding homogeneity, conformity, and dose to organs at risk. RESULTS: In the superior-inferior direction, larger displacements were found for EB compared to FB scans; anterior-posterior and right-left displacements were similar. With an initial rectum volume of < 115 cm(3), 90% of displacements at the posterior border were within a margin of 6 mm. The non-target volume irradiated in the high-dose area doubled in 3D-CRT versus IMRT plans (80 cm(3) vs. 38 cm(3) encompassed by the 95% isodose). Bladder dose was significantly lower with IMRT, but no advantage was found for the integral rectal dose. An adequate bladder filling was paramount to reduce the dose to the bladder. CONCLUSION: Postprostatectomy RT can be recommended with FB due to an improved CTV position consistency and a lower dose to the bladder. With improved non-target tissue and bladder volume sparing, IMRT is an option for dose escalation. However, this analysis did not find an advantage concerning the integral rectal dose with IMRT versus 3D-CRT.     

Testicular Dose in Prostate Cancer Radiotherapy

Purpose: To determine the dose received by the unshielded testicles during a course of 20-MV conventional external-beam radiotherapy for patients with localized prostate cancer. Critical evaluation of the potential impact on fertility and hormonal impairment in these patients according to the literature. Patients and Methods: The absolute dose received by the testicles of 20 randomly selected patients undergoing radiotherapy of prostate cancer was measured by on-line thermoluminescence dosimetry. Patients were treated in supine position with an immobilization cushion under their knees. A flexible tube, containing three calibrated thermoluminescence dosimeters (TLDs) was placed on top or underneath the testicle closest to the perineal region with a day-to-day alternation. The single dose to the planning target volume was 1.8 Gy. Ten subsequent testicle measurements were performed on each patient. The individual TLDs were then read out and the total absorbed dose was calculated. Results: The mean total dose (± standard deviation) measured in a series of 10 subsequent treatment days in all patients was 49 cGy (± 36 cGy). The calculated projected doses made on a standard series of 40 fractions of external-beam radiotherapy were 196 cGy (± 145 cGy). The results of this study are appraised with the available data in the literature. Conclusion: The dose received by the unshielded testes can be assessed as a risk for permanent infertility and impairment of hormonal function in prostate cancer patients treated with external-beam radiotherapy.     

Prostate Risk Index (PRIX) as a New Method of Risk Classification for Clinically Localized Prostate Cancer

PURPOSE: The aim of this study is (1) to develop a new method of risk classification for clinically localized prostate cancer; (2) to examine it in terms of compatibility with existing data such as nomograms; and (3) to compare it with existing risk-grouping methods. MATERIAL AND METHODS: The new grading system introduced here consists of three factors. The first is a prostate-specific antigen (PSA) of 4.1-10.0 ng/ml (score 0), 10.1-20.0 ng/ml (score 1), and >20.0 ng/ml (score 2). The second is a Gleason score (GS) of 6 (score 0), 7 (score 1), and 8-10 (score 2). The third is T classifications (UICC 2002) of T1c-T2a (score 0), T2b-T2c (score 1), and T3a (score 2). The sum of the three scores was named Prostate Risk Index (PRIX). Then, the compatibility of PRIX with the Partin Table, Kattan Nomogram, and Roach's formula was examined. At the same time, PRIX was compared with D'Amico, the National Comprehensive Cancer Network (NCCN), and Seattle classifications. RESULTS: PRIX 0 corresponded to 1-2% of pathologic lymph node involvement (pLN+) according to the Partin Table; PRIX 1 to 3-4%; PRIX 2 to 7-10%; PRIX 3 to 14-18%; PRIX 4 to 24-29%; PRIX 5 to 32-37%; and PRIX 6 to 42%. PRIX well separated the risks with relatively narrow ranges of probability, while D'Amico, NCCN, and Seattle classifications generally gave wide ranges especially for high-risk groups, both in the Partin Table and Kattan Nomogram. Roach's formula sometimes overestimated the risk compared to the Partin Table. CONCLUSION: PRIX fully corresponded to the Partin Table in terms of pLN+, and corresponded to the other nomograms better than any existing risk-grouping method. PRIX may thus function as a prognostic factor or contribute to patient selection in clinically localized prostate cancer.     

Health-Related Quality of Life Measurement in Long-Term Survivors and Outcome Following Radical Radiotherapy for Localized Prostate Cancer

PURPOSE: To report long-term outcomes in terms of health-related quality of life (HRQoL) and survival of a dose-escalating radiotherapy protocol and to validate a new disease-specific HRQoL instrument. PATIENTS AND METHODS: 189 consecutive men with prostate cancer were analyzed; 127 patients had T1-2 (1% T1, 66% T2) and 62 patients (33%) T3 tumors. The pelvic lymphatics were treated to a dose of 50 Gy by external-beam irradiation. The prostate dose was limited to 40 Gy using compensators. The prostate was treated to the total nominal dose of 70 Gy using high-dose-rate (HDR) brachytherapy. The fraction dose was 15 Gy in the McNeal zone (planning target volume [PTV] 1), while 8-9 Gy were applied in the entire prostate (PTV 2). The HRQoL of the 145 long-term survivors was assessed using the EORTC QLQ-C30 and a new prostate-specific instrument (PSM-G 1.0). The reliability of the instruments used and HRQoL scale scores were calculated. Uni-/multivariate analyses of variance were performed. RESULTS: At a mean follow-up of 6.5 years 86.3% of the patients were disease-free, and 78% were biochemically controlled. The mean Cronbach's alpha-values were 0.81 for the QLQ-C30, and 0.74 for the prostate-specific module. Univariate analyses of variance by T-stage, grading, prostata-specific antigen (PSA) status after therapy and adjuvant androgen suppression (AS) revealed that PSA elevation after irradiation and AS were associated with significantly diminished HRQoL. In multivariate analyses AS significantly lowered the HRQoL without survival benefit. CONCLUSION: The described radiotherapy regimen represents a curative and well-tolerated treatment for localized prostate cancer. The HRQoL assessment with both instruments used was reliable. Adjuvant AS and PSA elevation were associated with diminished HRQoL.     

Intensity-Modulated Radiation Therapy (IMRT) with Different Combinations of Treatment-Planning Systems and Linacs

PURPOSE: To compare different combinations of intensity-modulated radiation therapy (IMRT) system components with regard to quality assurance (QA), especially robustness against malfunctions and dosimetry. MATERIAL AND METHODS: Three different treatment-planning systems (TPS), two types of linacs and three multileaf collimator (MLC) types were compared: commissioning procedures were performed for the combination of the TPS Corvus 5.0 (Nomos) and KonRad v2.1.3 (Siemens OCS) with the linacs KD2 (Siemens) and Synergy (Elekta). For PrecisePLAN 2.03 (Elekta) measurements were performed for Elekta Synergy only. As record and verify (R&V) system Multi-Access v7 (IMPAC) was used. The use of the serial tomotherapy system Peacock (Nomos) was investigated in combination with the Siemens KD2 linac. RESULTS: In the comparison of calculated to measured dose, problems were encountered for the combination of KonRad and Elekta MLC as well as for the Peacock system. Multi-Access failed to assign the collimator angle correctly for plans with multiple collimator angles per beam. Communication problems of Multi-Access with both linacs were observed, resulting in incorrect recording of the treatment. All reported issues were addressed by the manufacturers. CONCLUSION: For the commissioning of IMRT systems, the whole chain from the TPS to the linac has to be investigated. Components that passed the commissioning in another clinical environment can have severe malfunctions when used in a new environment. Therefore, not only single components but the whole chain from planning to delivery has to be evaluated in commissioning and checked regularly for QA.