Comparing morbidity and cancer control after 3D-conformal (70/74 Gy) and intensity modulated radiotherapy (78/82 Gy) for prostate cancer.

PURPOSE: The purpose of this work was to compare toxicity and cancer control between patients with prostate cancer treated using three-dimensional conformal radiotherapy (3D-CRT) and those treated using intensity-modulated radiation therapy (IMRT). METHODS AND MATERIALS: A total of 553 patients with prostate cancer were treated with 3D-CRT 70-74 Gy (3D-CRT 70, 3D-CRT 74) or IMRT 78-82 Gy (IMRT 78, IMRT/SIB 82). Late toxicity was scored according to FC-RTOG/LENT criteria. Biochemical failure was defined using the Phoenix and ASTRO definitions. RESULTS: The 5-year risk of grade 2-4 genitourinary toxicity was 26.3 % (3D-CRT 70), 27.2 % (3D-CRT 74), 17.3 % (IMRT 78), and 25.1 % (IMRT/SIB 82) without statistical differences. The 5-year risk of grade 2-4 gastrointestinal toxicity was 19.4 % (3D-CRT 70), 42.1 % (3D-CRT 74), 20.5 % (IMRT 78), and 26.6 % (IMRT/SIB 82). The differences between 3D-CRT 74 and 3D-CRT 70 and between 3D-CRT 74 and IMRT 78 were statistically significant (log rank p = 0.03). The 5-year Phoenix PSA relapse-free survival (PSA-RFS) in low-risk, intermediate-risk, and high-risk patients treated using 3D-CRT were 89.4, 65.5, and 57.8 %, respectively. Patients treated with IMRT achieved the following results: 90.9, 89.4, and 83.9 %. Clinical relapse-free survival (C-RFS) in patients treated using 3D-CRT vs. IMRT for the aforementioned groups were 94.7 vs. 100 %, 86.8 vs. 98.6 %, and 84.4 vs. 94.5 %. Disease-free survival (DFS) for patients treated using 3D-CRT were 83.1, 70.9, and 71.5 %. The IMRT group reached 95.8, 89.1, and 87.6 %. The PSA-RFS for intermediate- and high-risk patients were statistically significant, while C-RFS and DFS were marginally better. CONCLUSION: Dose escalation with IMRT was associated with improved cancer control in intermediate- and high-risk patients in comparison with 3D-CRT, without compromising toxicity.

Late toxicity after conformal and intensity-modulated radiation therapy for prostate cancer: impact of previous surgery for benign prostatic hyperplasia.

OBJECTIVES: To retrospectively compare late toxicity of conventional-dose three-dimensional conformal radiation therapy (3D-CRT) and high-dose intensity-modulated radiation therapy (IMRT) for prostate cancer. METHODS: A total of 340 patients with T1-3 prostate cancer were treated with 3D-CRT (n = 228) and IMRT (n = 112). The median follow-up time was 5.9 years and 3.0 years, respectively. The prescription dose was 70 Gy for 3D-CRT and 78 Gy for IMRT. Late gastrointestinal (GI) and genitourinary (GU) toxicities were graded according to the Fox Chase modification of the Radiation Therapy Oncology Group and Late Effects Normal Tissue Task Force criteria. RESULTS: There was no difference between 3D-CRT and IMRT in the incidence of GI and GU toxicity at 3 years. On multivariate analysis, transurethral resection of prostate/open transvesical prostatectomy (TURP/TVPE) for benign prostatic hyperplasia, carried out before radiotherapy, significantly increased the risk of Grade >or=2 GU toxicity (risk ratio 1.88). Among patients who experienced TURP/TVPE, the 5-year actuarial likelihood of Grade 2-3 urinary incontinence was 23%, compared with 9% for those without prostate surgery (P = 0.01). CONCLUSIONS: Tolerance of 3D-CRT and IMRT was similar, despite the use of high radiation dose with IMRT. Previous TURP/TVPE increased the risk of GU toxicity.

Dose escalation in prostate radiotherapy up to 82 Gy using simultaneous integrated boost: direct comparison of acute and late toxicity with 3D-CRT 74 Gy and IMRT 78 Gy.

PURPOSE: To compare acute and late toxicity after three-dimensional conformal radiotherapy to the prostate to 74 Gy (3D-CRT) with intensity-modulated radiotherapy to 78 Gy (IMRT 78) and IMRT using simultaneous integrated boost to 82 Gy (IMRT/SIB 82). PATIENTS AND METHODS: 94 patients treated with 3D-CRT to the prostate and base of seminal vesicles to 74 Gy represented the first group. The second group consisted of 138 patients subjected to IMRT covering the prostate and base of seminal vesicles to 78 Gy. The last group was treated with IMRT using SIB. The prescribed doses were 82 Gy and 73.8 Gy in 42 fractions to the prostate and seminal vesicles. Late toxicity was prospectively scored according to the RTOG/FC-LENT scale. RESULTS: Acute gastrointestinal toxicity >or= grade 2 occurred in 35.1% of patients treated with 3D-CRT, in 16% subjected to IMRT 78, and in 7.7% receiving IMRT/SIB 82. Acute genitourinary toxicity >or= grade 2 was observed in 26.6% (3D-CRT), 33% (IMRT 78), and 30.7% (IMRT/SIB 82). At 3 years, the estimated cumulative incidence of grade 3 late gastrointestinal toxicity was 14% for 3D-CRT, 5% for IMRT 78, and 2% for IMRT/SIB 82. The difference became significant (log rank p = 0.02). The estimated cumulative incidence of grade 3 late genitourinary toxicity was 9% (3D-CRT), 7% (IMRT 78), and 6% (IMRT/SIB 82) without statistical differences (log rank p = 0.32) CONCLUSION: SIB enables dose escalation up to 82 Gy with a lower rate of gastrointestinal toxicity grade 3 in comparison with 3D-CRT up to 74 Gy.

IMRT with the use of simultaneous integrated boost in treatment of head and neck cancer: acute toxicity evaluation.

Acute toxicity has been evaluated in head and neck cancer patients treated with intensity-modulated radiotherapy using simultaneous integrated boost (SIB-IMRT). The basis of the treatment protocol is an irradiation in 30 fractions with a total dose: 66 Gy to the region of macroscopic tumor, 60 Gy to the region of high-risk subclinical disease and 54 Gy to the region of low-risk subclinical disease. Between December 2003 and September 2005, 38 patients with carcinoma of different locations in the head and neck region were irradiated. Five patients underwent concurrent chemotherapy (weekly cisplatin). Acute toxicity was evaluated according to Radiation Therapy Oncology Group toxicity scale for skin, mucous membrane, salivary glands, pharynx and esophagus and larynx. All 38 patients completed the therapy without urgency of interruption due to acute toxicity of radiotherapy. No patient experienced grade 4 toxicity. More severe toxicity was observed in patients with concurrent chemotherapy. The results confirm that the irradiation according to our SIB-IMRT protocol is a therapy with acceptable toxicity and there is a space for radiobiological enhancement of this regimen by concurrent chemotherapy, e.g. weekly cisplatin.

Is it reasonable to consider second-line chemotherapy in patients with hormone-refractory prostate cancer?

At present, no consensus exists regarding the use of second-line chemotherapy in patients with hormone-refractory prostate cancer (HRPC). A total of 23 patients with evidence of disease progression during or after first-line chemotherapy (epirubicin, etoposide, and dexamethasone) were included in this study. Two second-line treatments were administered throughout the study period (2000-2004) with 15/23 patients receiving carboplatin AUC 3 on day 1 and vinblastine 5 mg/m2 on day 1 of a 21-day cycle and 8/23 patients treated with docetaxel 50 mg/m2 on day 1 of a 21-day cycle. The latter regimen has been used since 2003. The prostate-specific antigen (PSA) level decreased by > or =50% in 3 of 23 patients, corresponding to an overall PSA response rate of 13% (95% confidence interval, 3-34%). The median time to biochemical progression was 9, 24 and 33 weeks, respectively. The median overall survival was 39 weeks (range, 15-73 weeks) with no difference between the two chemotherapy groups (p=0.08). A significant reduction of analgesic use was observed in 2 of 10 patients (20%) who required analgesics for cancer pain upon study entry. The major toxicity was grade 3 thrombocytopenia in 2 of 23 patients (9%). Both second-line treatments, a combination of carboplatin and vinblastine and a monotherapy with docetaxel, showed modest activity at subtoxic doses in patients with HRPC.

Comparison of rectal dose-volume constraints for IMRT prostate treatment planning.

The purpose of this paper is to compare different sets of rectal dose-volume constraints and to develop input criteria for the intensity-modulated radiation therapy (IMRT) of prostate cancer. The IMRI treatment plans were created using Varian planning system (CadPlan with Helios module) for ten patients with localized prostate cancer (isocenter dose 78 Gy). The posterior portion of rectum was contoured as an extra volume (help volume). Three sets of input parameters for rectum with gradually increasing priorities (25-50-75-90) were designed for the inverse treatment planning: 1. dose-volume constraints allowing no more than 50, 40, 20 and 10% of the rectum volume be irradiated to 50, 60, 70, and 75 Gy, respectively-volume-based plans, priorities 25-90 (V25-90 plans); 2. maximum dose constraint of 74.1 Gy for rectum-plans with limited maximum reactal dose, priorities 25-90 (M25-90 plans); 3. maximum dose constraint of 50 Gy for the help volume-plans with limited maximum dose for the help volume, priorities 25-90 (H25-90 plans). Dose homogeneity in the planning target volume (PTV) and the rectal volumes (RV) irradiated to 50, 60, 70, and 75 Gy (RV 50-75 Gy) were recorded. Rectum sparing improved for all the plans with increasing priority. While the M plans had the lowest RV 75 Gy values, the H plans gave the minimum RV 50-70 Gy values. Plans were considered acceptable if at least 98% of the PTV was treated to 95% of the prescribed dose. In particular plan groups, the V75, M75, and H50 plans, together with the V50+M75 and H50+M75 combined plans, satisfied this condition and yielded the lowest rectal doses. The H50+M75 combined plan allowed optimal sparing of rectum (RV 50 Gy 51.6%, RV 60 Gy 38.5%, RV 70 Gy 26.0%, and RV 75 Gy 9.1%, respectively). An optima set of dose-based rectal constraints (maximum rectal dose 74.1 Gy, maximum help volume dose 50 Gy) has been developed for Varian planning software. These parameters will constitute a starting point for the prostate IMRT plan optimization.

Prognostic impact of hemoglobin level prior to radiotherapy on survival in patients with glioblastoma.

PURPOSE: To evaluate prognostic factors in patients with glioblastoma treated with postoperative or primary radiotherapy. PATIENTS AND METHODS: From 1989 to 2000, a total of 100 patients underwent irradiation as part of their initial treatment for glioblastoma. All patients had undergone surgery or biopsy followed by conventional external-beam radiotherapy. 85 patients who received the planned dose of irradiation (60 Gy in 30 fractions) were analyzed for the influence of prognostic factors. 73/85 (86%) of patients were given postoperative irradiation, while 12/85 (14%) of patients were primarily treated with radiotherapy after biopsy. RESULTS: The median overall survival was 10.1 months (range, 3.7-49.8 months), the 1- and 2-year survival rates were 41% and 5%, respectively. Univariate analysis revealed age < or = 55 years (p < 0.001), pre-radiotherapy hemoglobin (Hb) level > 12 g/dl (p = 0.009), and pre-radiotherapy dose of dexamethasone < or = 2 mg/day (p = 0.005) to be associated with prolonged survival. At multivariate analysis, younger age (p < 0.001), higher Hb level (p = 0.002), lower dose of dexamethasone (p = 0.026), and a hemispheric tumor location (p = 0.019) were identified as independent prognostic factors for longer survival. The median survival for patients with an Hb level > 12 g/dl was 12.1 months compared to 7.9 months for those with a lower Hb level. Contingency-table statistics showed no significant differences for the two Hb groups in the distribution of other prognostic factors. CONCLUSION: The results indicate that lower Hb level prior to radiotherapy for glioblastoma can adversely influence prognosis. This finding deserves further evaluation.

Bi-weekly epirubicin, etoposide and low-dose dexamethasone for hormone-refractory prostate cancer.

BACKGROUND: Recent studies have demonstrated the efficacy and favorable toxicity profile of chemotherapy regimens given at lower doses and frequent intervals. The aim of our study was to evaluate the efficacy and toxicity of a bi-weekly chemohormonal regimen consisting of epirubicin, etoposide, and low-dose dexamethasone (EED) in patients with hormone-refractory prostate cancer (HRPC). METHODS: We treated a total of 32 patients who had failed hormonal therapy and antiandrogen withdrawal. Chemotherapy was given every 2 weeks and consisted of epirubicin (30 mg/m2 intravenously, day 1) and etoposide (50 mg/m2 orally, days 1-7). Dexamethasone (1.5 mg orally, every other day) was given continuously until disease progression. Twenty patients (63%) had received prior treatment with estramustine phosphate. Each patient's pain response was evaluated according to analgesic use. Toxicity was graded using the Common Toxicity Criteria (version 2.0). RESULTS: Prostate-specific antigen (PSA) levels showed a decline of 50% or greater in 16 of 32 patients (50%, 95% confidence interval [CI], 32-68%) with a median time to biochemical progression of 5 months (range, 4-9 months). The median survival for all patients was 10.5 months (range, 3-35 months). Four of 10 patients (40%) with measurable soft tissue lesions achieved partial response according to standard criteria. Eleven of 23 symptomatic patients (48%, 95% CI, 27-69%) experienced an improvement in pain with a median duration of 6 months. The regimen was tolerated well by the patients, with only four patients (12%) having grade 3 leukopenia. CONCLUSION: Chemohormonal EED regimen proved to be active and well-tolerated in patients with HRPC.