[en] Purpose: To compare dose distribution for two techniques of 3-dimensional conformal radiotherapy (RT): 6-field technique (6F) and 2-dynamic arc therapy (2DA). Methods and materials: Thirty nonmetastatic prostate cancer patients were included. In each patient, two treatment plans were prepared: with six coplanar fields (45 deg., 90 deg., 135 deg., 225 deg., 270 deg., 315 deg.) and with two dynamic lateral 100^o-wide arcs (40-140^o, 220-320^o). Dose-volume histograms (DVHs) were computed and mean area under curve (AUC) values were calculated for the DVHs of Planning Target Volume (PTV), rectum, urinary bladder and femoral heads. Doses given to 30% of rectum (DR₃), to 60% of rectum (DR₆), to 50% of bladder (DB₅), to 50% of femoral head (DF₅) and to 95% of PTV (DPTV₉₅) were reported as a percentage of the total dose. Results: Mean DR₃ and DR₆ for 6F and 2DA were 75.8%, 51.5% and 72.2%, 37.2%, respectively. Mean DB₅ for 6F and 2DA were 68% and 64.2%, respectively. Mean right DF₅ for 6F and 2DA were 35.4% and 45.5%, respectively. Mean DPTV₉₅ for 6F and 2DA were 99% and 99.2%, respectively. Mean AUCs of DVHs of rectum and urinary bladder were significantly higher for 6F (this was more evident for small PTV and in the intermediate dose range). Mean AUC of DVHs of PTV and femoral heads were significantly higher for 2DA. Conclusions: Both 6F and 2DA offer good dose distribution for PTV. 2DA allows for significantly better sparing of rectum and urinary bladder with slightly worse femoral head dose distribution. Further study is warranted in order to establish the clinical relevance of these differences

[en] Purpose: To analyze the correlation between acute and late injury in 973 prostate cancer patients treated with radiotherapy and to evaluate the effect of patient-, tumor-, and treatment-related variables on toxicity. Methods and Materials: Of the 973 patients, 542 and 431 received definitive or postprostatectomy radiotherapy, respectively. Three-dimensional conformal radiotherapy included a six-field technique and two-dynamic arc therapy. Toxicity was classified according to the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria. The correlation between acute and late toxicity (incidence and severity) was assessed. Results: Multivariate analysis showed that age ≤65 years (p = .06) and use of the three-dimensional, six-field technique (p <.0001) correlated significantly with greater acute rectal toxicity. The three-dimensional, six-field technique (p = .0002), dose >70 Gy (p = .014), and radiotherapy duration (p = .05) correlated with greater acute urinary toxicity. Acute rectal toxicity (p <.0001) was the only factor that correlated with late rectal injury on multivariate analysis. Late urinary toxicity correlated with acute urinary events (p <.0001) and was inversely related to the use of salvage radiotherapy (p = .018). A highly significant correlation was found between the incidence of acute and late events for both rectal (p <.001) and urinary (p <.001) reactions. The severity of acute toxicity (Grade 2 or greater) was predictive for the severity of late toxicity for both rectal and urinary events (p <.001). Conclusion: The results of our study have shown that the risk of acute reactions depends on both patient-related (age) and treatment-related (dose, technique) factors. Acute toxicity was an independent significant predictor of late toxicity. These findings might help to predict and prevent late radiotherapy-induced complications.

[en] Purpose: to analyze the reliability of different methods used in evaluating the risk of late rectal toxicity. Patients and methods: the treatment plans of 57 patients treated at the authors' institute between September 1999 and September 2000 for localized prostate cancer using three-dimensional conformal radiotherapy (3D-CRT) were analyzed retrospectively. The expected rate of late rectal toxicity was analyzed (a) by means of the dose-volume histogram (DVH) constraints; (b) by calculating the normal-tissue complication probability (NTCP) using the Lyman-Kutcher-Burman (LKB) model with the radiobiological parameters of either Emami (1991; for toxicity of grade ≥ 2) or Rancati (2004; for toxicity of grade ≥ 2 and ≥ 3). Patients were divided into high-/low-risk (HR/LR) groups and the results were compared to the clinical outcome. Results: (a) The HR percentages were 24% and 5% for radical and postsurgical 3D-CRT, respectively. When applying high-dose constraints only, HR percentages were 18% and 5%, respectively. (b) In the case of the NTCP (grade ≥ 2), Emami (1991) HR rates were 16% and 11%, and Rancati (2004) HR rates 29% and 11%, for radical and postsurgical treatment, respectively. Only one case with higher-grade toxicity was found. The reported clinical toxicity was 17.8% and 6.7% for grade ≥ 2 toxicity, and 3.7% and 0.7% for grade ≥ 3 toxicity, for radical and postsurgical treatment, respectively. Conclusion: this study demonstrated that there is an agreement between the toxicity rate evaluated by DVH constraints and by the LKB model and the clinical outcome. In this case, the use of the LKB model can be as reliable as the use of DVH constraints. (orig.)

[en] To assess the dosimetric and clinical implication when applying the full bladder protocol for the treatment of the localized prostate cancer (PCA). A total of 26 consecutive patients were selected for the present study. Patients underwent two series of CT scans: the day of the simulation and after 40 Gy. Each series consisted of two consecutive scans: (1) full bladder (FB) and (2) empty bladder (EB). The contouring of clinical target volumes (CTVs) and organs at risk (OAR) were compared to evaluate organ motion. Treatment plans were compared by dose distribution and dose-volume histograms (DVH). CTV shifts were negligible in the laterolateral and superior-inferior directions (the maximum shift was 1.85 mm). Larger shifts were recorded in the anterior-posterior direction (95% CI, 0.83-4.41 mm). From the dosimetric point of view, shifts are negligible: the minimum dose to the CTV was 98.5% (median; 95%CI, 95-99%). The potential advantage for GU toxicity in applying the FB treatment protocol was measured: the ratio between full and empty bladder dose-volume points (selected from our protocol) is below 0.61, excluding the higher dose region where DVHs converge. Having a FB during radiotherapy does not affect treatment effectiveness, on the contrary it helps achieve a more favorable DVH and lower GU toxicities.

[en] To assess the efficacy and safety of salvage stereotactic body radiation therapy (SBRT) in patients with biopsy-proven local prostate cancer recurrence after radiation therapy.

[en] Purpose: To evaluate the outcome of postoperative radiotherapy (PORT) and salvage RT (SART) using a three-dimensional conformal two-dynamic arc (3D-ART) or 3D six-field technique in 431 prostate cancer patients. Methods and Materials: Of the 431 patients, 258 underwent PORT (started <6 months after radical prostatectomy) and 173 underwent SART because of biochemical failure after radical prostatectomy. The median patient age, preoperative prostate-specific antigen level, and Gleason score was 66 years, 9.4 ng/mL, and 7, respectively. The median radiation dose was 70 Gy in 35 fractions for both PORT and SART. The 3D six-field and 3D-ART techniques were used in 25.1% and 74.9% of patients, respectively. Biochemical failure was defined as a post-RT prostate-specific antigen nadir plus 0.1 ng/mL. Results: Acute toxicity included rectal events (PORT, 44.2% and 0.8% Grade 1-2 and Grade 3, respectively; SART, 42.2% and 1.2% Grade 1-2 and Grade 3, respectively) and urinary events (PORT, 51.2% and 2.3% Grade 1-2 and Grade 3-4, respectively; SART, 37.6% and 0% Grade 1-2 and Grade 3, respectively). Late toxicity also included rectal events (PORT, 14.7% and 0.8% Grade 1-2 and Grade 3-4, respectively; SART, 15.0% and 0.6% Grade 1-2 and Grade 3, respectively) and urinary events (PORT, 28.3% and 3.7% Grade 1-2 and Grade 3-4, respectively; SART, 19.3% and 0.6% Grade 1-2 and Grade 3, respectively). After a median follow-up of 48 months, failure-free survival, including biochemical and clinical failure, was significantly longer in the PORT patients (79.8% vs. 60.5%, p < 0.0001). Multivariate analysis showed that a prostate-specific antigen level postoperatively but before RT of ≥0.2 ng/mL (p < 0.001), Gleason score >6 (p = 0.025) and use of preoperative androgen deprivation (p = 0.002) correlated significantly with shorter failure-free survival. Multivariate analysis showed that PORT and the 3D-ART technique correlated with greater late urinary toxicity. Conclusion: PORT and early referral for SART offer better disease control after radical prostatectomy. The greater urinary toxicity occurring after PORT and 3D-ART requires further investigation to improve the therapeutic index.

[en] Purpose: To present the results of dose escalation using three-dimensional conformal dynamic arc radiotherapy (3D-ART) for prostate cancer. Methods and Materials: Five hundred and forty two T1-T3N0M0 prostate cancer patients were treated with 3D-ART. Dose escalation (from 76 Gy/38 fractions to 80 Gy/40 fractions) was introduced in September 2003; 32% of patients received 80 Gy. In 366 patients, androgen deprivation was added to 3D-ART. Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria and Houston definition (nadir + 2) were used for toxicity and biochemical failure evaluation, respectively. Median follow-up was 25 months. Results: Acute toxicity included rectal (G1-2 28.9%; G3 0.5%) and urinary events (G1-2 57.9%; G3-4 2.4%). Late toxicity included rectal (G1-2 15.8%; G3-4 3.1%) and urinary events (G1-2 26.9%; G3-4 1.6%). Two-year failure-free survival and overall survival rates were 94.1% and 97.9%, respectively. Poor prognostic group (GS, iPSA, T), transurethral prostate resection, and dose >76 Gy showed significant association to high risk of progression in multivariate analysis (p = 0.014, p = 0.045, and p 0.04, respectively). The negative effect of dose >76 Gy was not observed (p 0.10), when the analysis was limited to 353 patients treated after September 2003 (when dose escalation was introduced). Higher dose was not associated with higher late toxicity. Conclusions: Three-dimensional-ART is a feasible modality allowing for dose escalation (no increase in toxicity has been observed with higher doses). However, the dose increase from 76 to 80 Gy was not associated with better tumor outcome. Further investigation is warranted for better understanding of the dose effect for prostate cancer

[en] We report on 14 patients treated with linac- or robotic image-guided stereotactic radiotherapy for isolated lymph node recurrence from prostate cancer, up to the mean dose of 30 Gy/3 fractions. At the mean follow-up of 18.6 months, five patients experienced clinical out-field progression. Toxicity was minimal. Further investigation is warranted in order to identify the patients that benefit most from this treatment modality and to define the optimal association of such local approach with androgen deprivation. Hopefully, effective local therapy might reduce the burden of systemic therapies given to the recurrent/metastatic prostate cancer patients.

[en] Purpose: To report the acute and preliminary data on late toxicity of a pilot study of boost with electron intraoperative therapy followed by hypofractionated external beam radiotherapy (HEBRT) of the whole breast. Methods and Materials: Between June 2004 and March 2007, 211 women with a diagnosis of early-stage breast cancer were treated with breast-conserving surgery. During surgery, an electron intraoperative therapy boost of 12 Gy was administered to the tumor bed. Adjuvant local treatment was completed with HEBRT, consisting of a course of 13 daily fractions of 2.85 Gy to the whole breast to a total dose of 37.05 Gy. Acute toxicity of the breast was evaluated at the end of HEBRT and at 1 month of follow-up. Late toxicity was recorded at 6 and 12 months of follow-up. Results: We report the data from 204 patients. The maximal acute skin toxicity was observed at the end of HEBRT (182 patients evaluable) with 7 (3.8%) Grade 3, 52 (28.6%) Grade 2, 123 (67.6%) Grade 1, and no Grade 0 or Grade 4 cases. A total of 108 patients were evaluated for late toxicity. The recorded late skin toxicity was Grade 4 in 1 patient (0.9%), Grade 3 in 1 patient, and Grade 2 or less in 106 patients (98.2%). Conclusions: The results of this study have shown that electron intraoperative therapy followed by HEBRT allows for the delivery of a high dose to the tumor bed and an adequate dose to the whole breast. This treatment is feasible, compliance is high, and the rate of acute toxicity and the preliminary data on chronic toxicity seem acceptable

[en] Purpose: To evaluate the outcome of robotic CyberKnife (Accuray, Sunnyvale, CA)–based stereotactic radiotherapy (CBK-SRT) for isolated recurrent primary, lymph node, or metastatic prostate cancer. Methods and Materials: Between May 2007 and December 2009, 34 consecutive patients/38 lesions were treated (15 patients reirradiated for local recurrence [P], 4 patients reirradiated for anastomosis recurrence [A], 16 patients treated for single lymph node recurrence [LN], and 3 patients treated for single metastasis [M]). In all but 4 patients, [¹¹C]choline positron emission tomography/computed tomography was performed. CBK-SRT consisted of reirradiation and first radiotherapy in 27 and 11 lesions, respectively. The median CBK-SRT dose was 30 Gy in 4.5 fractions (P, 30 Gy in 5 fractions; A, 30 Gy in 5 fractions; LN, 33 Gy in 3 fractions; and M, 36 Gy in 3 fractions). In 18 patients (21 lesions) androgen deprivation was added to CBK-SRT (median duration, 16.6 months). Results: The median follow-up was 16.9 months. Acute toxicity included urinary events (3 Grade 1, 2 Grade 2, and 2 Grade 3 events) and rectal events (1 Grade 1 event). Late toxicity included urinary events (3 Grade 1, 2 Grade 2, and 2 Grade 3 events) and rectal events (1 Grade 1 event and 1 Grade 2 event). Biochemical response was observed in 32 of 38 evaluable lesions. Prostate-specific antigen stabilization was seen for 4 lesions, and in 2 cases prostate-specific antigen progression was reported. The 30-month progression-free survival rate was 42.6%. Disease progression was observed for 14 lesions (5, 2, 5, and 2 in Groups P, A, LN, and M respectively). In only 3 cases, in-field progression was seen. At the time of analysis (May 2010), 19 patients are alive with no evidence of disease and 15 are alive with disease. Conclusions: CyberKnife-based stereotactic radiotherapy is a feasible approach for isolated recurrent primary, lymph node, or metastatic prostate cancer, offering excellent in-field tumor control and a low toxicity profile. Further investigation is warranted to identify the patients who benefit most from this treatment modality. The optimal combination with androgen deprivation should also be defined.