The Role of Adjuvant Radiotherapy in the Treatment of Breast Cancer.

The role of postmastectomy radiotherapy and regional nodal irradiation after radical mastectomy is defined in high-risk patients with locally advanced tumors, positive margins, and unfavorable biology. The benefit of postmastectomy radiotherapy in intermediate-risk patients (T3N0 tumors) remains a matter of controversy. It has been demonstrated that radiotherapy after breast-conserving surgery lowers the locoregional recurrence rate compared with surgery alone and improves the overall survival rate. In patients with four or more positive lymph nodes or extracapsular extension, regional lymph node irradiation is indicated regardless of the surgery type (breast-conserving surgery or mastectomy). Despite the consensus that patients with more than three positive lymph nodes should be treated with radiotherapy, there is controversy regarding the recommendations for patients with one to three involved lymph nodes. In patients with N0 disease with negative findings on axillary surgery, there is a trend to administer regional lymph node irradiation in patients with a high risk of recurrence. In patients treated with neoadjuvant systemic therapy and mastectomy, adjuvant radiotherapy should be administered in cases of clinical stage III and/or ≥ypN1. In patients treated with neoadjuvant systemic therapy and breast-conserving surgery, postoperative radiotherapy is indicated irrespective of pathological response.

Special Techniques of Adjuvant Breast Carcinoma Radiotherapy.

Modern radiotherapy techniques are designed to permit reduced irradiation of healthy tissue, resulting in a diminished risk of adverse effects and shortened recovery times. Several randomized studies have demonstrated the benefits of increased dosage to the tumor bed area in combination with whole breast irradiation (WBI). Conventional WBI treatment following breast-conserving procedures, which required 5-7 weeks of daily treatments, has been reduced to 3-4 weeks when using hyperfractionated regimens. The dosage administration improves local control, albeit with poorer cosmesis. The method of accelerated partial breast irradiation (APBI) shortens the treatment period whilst reducing the irradiated volume. APBI can be delivered using intraoperative radiation, brachytherapy, or external beam radiotherapy. Currently available data support the use of external beam partial breast irradiation in selected patients. Modern radiotherapy techniques make it possible to achieve favorable cosmesis in most patients undergoing immediate breast reconstruction surgery, and studies confirm that current methods of external beam radiation allow an acceptable coverage of target volumes both in the reconstructed breast and in the regional lymphatic nodes.

Image-guided radiation therapy produces lower acute and chronic gastrointestinal and genitourinary toxicity in prostate cancer patients.

PURPOSE: This paper compares individual radiation therapy techniques used for prostate cancer and their benefits in clinical practice. METHODS: We retrospectively analyzed 921 patients with localized prostate tumors treated between 1997 and 2012. We divided the patients into four groups according to the selected treatment technique (conformal radiation therapy [3DCRT], intensity-modulated radiation therapy [IMRT], image-guided radiation therapy [IGRT], and volumetric-modulated arc therapy [VMAT]) and evaluated the incidence of acute and chronic gastrointestinal (GI) and genitourinary (GU) toxicity. RESULTS: The incidence of grade 2 or greater acute GU and GI toxicity was significantly higher among techniques other than IGRT (p˂0.001). We found the same results in the case of grade 3 or greater acute GU toxicity (p˂0.001). Grade 3 or higher acute GI toxicity occurred only in one patient treated by 3DCRT. Cumulative late GI toxicity of grade 2 or higher and grade 3 or higher was recorded over 3 years significantly more frequently among non-IGRT techniques as compared to IGRT (p˂0.001). As regards GU toxicity, we found significantly higher incidence only for grade 2 or higher (p˂0.001), not for grade 3 or higher. No occurrence of grade 4 toxicity was recorded. The greatest incidence of patients without acute and chronic GI/GU toxicity was recorded in connection with VMAT. CONCLUSION: IGRT demonstrated a pronounced reduction in acute and chronic GU and GI toxicity as compared to non-IGRT techniques in the treatment of localized prostate cancer.

Autologous dendritic cell-based immunotherapy (DCVAC/LuCa) and carboplatin/paclitaxel in advanced non-small cell lung cancer: A randomized, open-label, phase I/II trial.

PURPOSE: To investigate the efficacy and safety of an active cellular immunotherapy (DCVAC/LuCa) and chemotherapy in patients with stage IV non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: SLU01 was a multicenter, open-label, parallel-group, randomized, phase I/II trial. NSCLC patients were randomized in a ratio of 1:1:1 to receive: DCVAC/LuCa and chemotherapy (carboplatin and paclitaxel; Group A); DCVAC/LuCa, chemotherapy, pegylated interferon-α2b, and hydroxychloroquine (Group B); or chemotherapy alone (Group C). DCVAC/LuCa was administered subcutaneously every 3-6 weeks (up to 15 doses). The primary endpoint was overall survival (OS). During the study, enrollment into Group B was discontinued for strategic reasons. RESULTS: Forty-five patients were randomized to Group A, 29 patients to Group B, and 38 patients to Group C. The median OS in the modified intention-to-treat (mITT) population was 3.7 months longer in Group A than in Group C (15.5 vs. 11.8 months; p = 0.0179; hazard ratio = 0.54; 95% confidence interval: 0.32-0.91). This OS effect was consistent across subgroups of the mITT population (females, males, current smokers, former smokers, and patients with non-squamous and squamous cell histology). The most common treatment-emergent adverse events of any grade reported in Groups A, B, and C, respectively, were neutropenia (50.0%, 29.6%, and 20.6%), fatigue (40.0%, 18.5%, and 20.6%), anemia (35.0%, 44.4%, and 32.4%), paresthesia (27.5%, 25.9%, and 17.6%), and alopecia (25.0%, 29.6%, and 41.2%). CONCLUSION: DCVAC/LuCa in combination with carboplatin and paclitaxel extended OS and was well tolerated.

Controversies of radiotherapy in human epidermal growth factor receptor (HER)-2 positive breast cancer patients.

Tumor biology plays a crucial role in the systemic treatment, specifically in HER2-positive tumors. Distinct biological behavior of breast cancer subtypes is associated with different rates of locoregional recurrence (LRR). HER2- positive breast cancer patients treated with surgery in combination with radiation, without trastuzumab have poor outcome, including high LRR. The efficacy of radiotherapy in HER-2-positive breast cancer appears to be associated with the expression of estrogen receptors. In patients with HER-2-positive breast cancer, studies conducted before the introduction of trastuzumab indicated higher benefit of adjuvant radiation in patients with hormone receptor-positive tumors compared to patients with tumors not expressing hormone receptors. The introduction of agents targeting HER-2 has transformed the management of these patients, resulting in improved outcomes. The data of clinical studies show that the administration of trastuzumab as part of a multimodality approach (with radiation based on standard guidelines) results in improved outcomes, including lower locoregional recurrence. The risk of cardiac toxicity associated with radiation to the heart and administration of potential cardiotoxic trastuzumab is not clear. In patients treated concomitantly with regional lymph node irradiation and anti-HER-2 agents after prior anthracycline-based chemotherapy minimizing the dose to the myocardium, e.g. respiratory gating or proton beam radiotherapy, have been suggested.

Impact of Hormone Receptor Status on the Behaviour of HER2+ Breast Cancer.

BACKGROUND/AIM: The study aimed to evaluate differences in the overall survival of HER2+ breast cancer patients treated with regard to their hormone receptors negativity or positivity. We evaluated a cohort of patients treated with trastuzumab in the Czech Republic. PATIENTS AND METHODS: The present study is a retrospective analysis of patients whose data were recorded in a nationwide non-interventional, post-authorisation database BREAST. After propensity score matching of data, the cohort included 4,532 patients. RESULTS: A significant difference in overall survival (OS) of the entire cohort was found between patients with and without hormone dependence. The OS was significantly higher in the group of patients with hormone receptor-positive (HR+) tumours in the following cohorts: patients treated with neoadjuvant therapy, patients with advanced disease, G2 tumours, stage III and IV and in patients with stage II and III of G2 tumours. CONCLUSION: Increased OS rates were found in several subgroups of patients with HR+/HER2+ tumours compared to those with HR-/HER2+ tumours. Better outcomes of HR+/HER2+ patients were only observed in the first four/five years of follow-up, and the differences disappeared over time.

Giant locally advanced and metastatic squamous cell skin carcinoma of head and neck region: case report.

INTRODUCTION: At the present time, the skin tumors are among the most common cancers. Optimal therapy is based on the extent of the disease and the age of the patient. The need for radiotherapy occurs for inoperable locally advanced tumors and in the event of failure, salvage surgery is applied. MATERIALS AND METHODS: We provided a case report of an older patient with giant squamous cell skin carcinoma and a review of published articles. RESULTS: We present a rare case of giant squamous cell skin carcinoma with metastatic satellite tumors that was primarily treated with curative radiotherapy. Five months after radiotherapy, a recurrent tumor was detected at the site of origin and the treatment was completed by salvage surgery. Full remission was achieved for four years. CONCLUSION: Despite the seemingly incurable finding it is always necessary to consider radical treatment regardless of the patient´s age. Curative treatment could achieve long term remission in the group of older patients.

Audio-visual navigation reduces treatment time in deep-inspiration breath hold radiotherapy.

AIMS: The purpose of this study was to compare the treatment times for deep-inspiration breath hold with and without audio-visual (A-V) navigation. METHODS: We measured the real treatment time in 60 patients with breast cancer undergoing postoperative radiotherapy. Thirty consecutive patients were treated without deep-inspiration breath hold (DIBH) and another 30 patients using deep-inspiration breath hold (10 patients with DIBH only, 10 patients with DIBH using visual feedback and 10 patients with DIBH using visual feedback following breath training). The treatment time was relativized to number of fields and 100 monitor units (MU). The independent t-test was used to analyse differences between cohorts. RESULTS: The mean treatment time for patients without DIBH was 46.5 seconds per field and 90.9 seconds per 100 MU, for DIBH only 92.3 and 170.2 seconds, for DIBH with audio-visual navigation 68.1 and 133.8 seconds, and for DIBH with A-V feedback including breath training 66.1 and 132.5 seconds. The treatment times for patients treated using DIBH with visual navigation were significantly shorter in comparison with patients without visual feedback. We were not able to prove any significant benefit for breath training in terms of reducing the treatment time. CONCLUSION: Audio-visual navigation enables to significantly reduce the treatment time in comparison with DIBH without A-V feedback.

Therapeutic significance of hormone receptor positivity in patients with HER-2 positive breast cancer.

Breast cancer with high expression of human epidermal growth factor receptor (HER)-2 represents a biologically and clinically heterogeneous group of neoplastic disorders. Importantly, hormone receptor expression has an effect on biological properties and affects the selection of therapies. On the basis of molecular genetics, four principal subtypes, including luminal A, luminal B, HER2-enriched (HER-2-E), and basal-like can be distinguished. Breast tumors characterized by HER-2 positivity and simultaneous expression of hormone receptors, triple positive breast cancers (TPBC) are of increasing interest owing to the unique biological characteristics associated with complex interactions between HER-2 and hormone receptor signaling pathways. Interactions between hormone receptors and HER-2 explain the decreased efficacy of hormonal therapy in comparison with HER-2-negative patients. The expression of estrogen receptors in HER-2 positive tumors may also be associated with resistance to anti-HER-2 treatment. Multiple available therapeutic options, including hormonal therapy, anti-HER-2 agents and cytotoxic drugs explain favorable prognosis of TPBC. Escalation and de-escalation therapeutic strategies that could result in lower toxicities are being investigated as well as combinations of anti-HER-2 agents with hormonal therapy, immunotherapy, cyclin dependent kinase 4/6 and phosphatidyl inositol-3-kinase inhibitors. Distinction between subtypes of HER-2-positive breast cancer and treatment diversification may result in improved outcomes in TPBC. A response to neoadjuvant therapy may serve in the tailoring of therapy management.

Tumor bed radiotherapy in women following breast conserving surgery for breast cancer-safety margin with/without image guidance.

Image guided radiation therapy (IGRT) enables the achievement of higher precision in radiation delivery, a reduction in safety margins and a reduced risk of toxicity in healthy tissues. The present study investigated the magnitude of safety margins for the radiation boost setup on skin marks or metal clips implanted into the tumor bed during breast cancer surgery. One hundred eighty-four patients after breast conserving surgery with implanted metal clips into tumor bed were analyzed. The present study investigated the difference in safety margin required for the treatment setup on skin marks and metal clips. The skin marks were created using a positioning laser system in the treatment room. Metal clips implanted in the tumor bed were registered using IGRT with kilovoltage X-rays in orthogonal projection. Treatment setup was performed during free breathing. The safety margin corresponding to the planning target volume (PTV) was calculated from the recorded data. Calculated safety margins for the treatment setup on skin marks were 9.4, 11.1 and 11.1 mm in the anteroposterior, craniocaudal, and laterolateral directions, respectively. Corresponding safety margins with the use of IGRT and metal clips registration were 4.7, 5.1 and 5.9 mm, respectively. The safe PTV margin was 12 mm using setup on skin marks without IGRT, whereas a 6-mm margin was sufficient with the use of metal clip-based IGRT with daily online correction. IGRT has been adopted as the standard treatment method within the Oncology Centre of Multiscan and Pardubice Hospital (Pardubice, Czech Republic).

Interfraction variation in prostate cancer - analysis of 11726 cone-beam CT.

PURPOSE: To investigate the setup margins in prostate cancer treatment without using daily online repositioning methods. METHODS: We analysed the data from patients treated with curative-intend radiotherapy. Each patient underwent a series of pretreatment online localizations during daily setup using conebeam CT. The skin-prostate shifts and bone-prostate shifts were recorded in anteroposterior (AP), craniocaudal (CC), and laterolateral (LL)direction. The safety margins based on van Herk equation (2.5Σ+0.7σ) were calculated and the correlations between margins and various patient characteristics and prostate locations were investigated. RESULTS: A total of 307 patients were included, representing 11,726 localisations resulting in 70,356 shifts. The man skin-prostate setup inaccuracy was 0.8 ± 5.4mm in AP, 1.3 ± 4.8mm for CC, and 0.1 ± 5.6mm in LL direction. The man bone-prostate setup inaccuracy was 0.4 ± 3.3mm in AP, 0.1 ± 2.5mm for CC, and 0.1 ± 1.4mm in LL direction. According to van Herk equation, clinical target volume (CTV)-planning target volume (PTV) margins of 11.4, 10.6, and 11.8 mm (AP, CC, and LL, respectively) would be required for setup using skin markers and margins of 7.0, 4.7, and 2.1mm would be necessary for setup using bone structures. The average rectal area < 11cm(2) and volume of bladder > 300 cm(3) were associated with smaller CTV-PTV margins for setup using bone structures. The largest margins (15.8 mm in LL direction) were needed in patients with body mass index (BMI) > 35 using skin markers. CONCLUSIONS: Our results confirm that the commonly used CTV-PTV margins are inadequate.

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.

Searching for an appropriate image-guided radiotherapy method in prostate cancer--implications for safety margin.

AIMS AND BACKGROUND: The aim of the study was to compare the safety margin width using skin marks, pelvic skeleton-based targeting and adaptive protocol combining cone-beam computed tomography and kilovoltage image matching. METHODS: A total of 434 consecutive patients were treated by image-guided radiotherapy from November 2008 to April 2012. An adaptive protocol combining cone-beam computed tomography and kilovoltage image matching with individualized safety margin calculation according to the Van Herk method was used in a total of 201 patients. The remaining 233 patients had their setup corrected using cone-beam computed tomography daily. RESULTS: Analysis of the 3,137 cone-beam computed tomography images (201 patients) revealed that the margins between the clinical target volume and planning target volume with skin marks registration should be 1.24 cm in the anteroposterior, 0.98 cm in the craniocaudal, and 1.03 cm in the laterolateral direction. Considering pelvic skeleton-based setup, values of the clinical target volume and planning target volume margins in the anteroposterior, craniocaudal and laterolateral axis were 0.79 cm, 0.41 cm, and 0.19 cm, respectively. In a group of 8,872 cone-beam computed tomography images (233 patients) using CBCT assessment, the calculated margins between clinical target volume and planning target volume with skin marks were 1.15 cm in anteroposterior, 1.06 in craniocaudal, and 1.19 in laterolateral directions. Considering the pelvic skeleton-based setup, the corresponding values were 0.74 cm, 0.51 cm, and 0.25 cm. With the adaptive technique, the margins of most patients in the anteroposterior, craniocaudal, and laterolateral axes were 6 mm, 6 mm, and 6 mm or 8 mm, 6 mm, and 6 mm, respectively. CONCLUSIONS: The adaptive protocol combining cone-beam computed tomography and kilovoltage image matching or daily cone-beam computed tomography allowed us to substantially reduce the safety margins compared with skin marks targeting.

Statistical analysis of dose-volume profiles and its implication for radiation therapy planning in prostate carcinoma.

PURPOSE: The study aimed to analyze the dose-volume profiles of 3-dimensional radiation therapy (3D-CRT) and intensity modulated RT (IMRT) in the treatment of prostate carcinoma and to specify the profiles responsible for the development of gastrointestinal (GI) toxicity. METHODS AND MATERIALS: In the period 1997 to 2007, 483 patients with prostate carcinoma in stage T1-3 N0 (pN0) M0 were treated with definitive RT. Two groups of patients were defined for the analysis: the 3D-CRT group (n=305 patients) and the IMRT group (n=178 patients). In the entire cohort of 483 patients, the median follow-up time reached 4.4 years (range, 2.0-11.7 years). The cumulative absolute and relative volumes of irradiated rectum exposed to a given dose (area under the dose-volume curve, AUC) were estimated. The receiver operating characteristic analysis was then used to search for the optimal dose and volume cutoff points with the potential to distinguish patients with enhanced or escalated toxicity. RESULTS: Despite the application of high doses (78-82 Gy) in the IMRT group, GI toxicity was lower in that group than in the group treated by 3D-CRT with prescribed doses of 70 to 74 Gy. Both RT methods showed specific rectal dose-volume distribution curves. The total AUC values for IMRT were significantly lower than those for 3D-CRT. Furthermore, IMRT significantly decreased the rectal volume receiving low to intermediate radiation doses in comparison with 3D-CRT; specific cutoff limits predictable for the level of GI toxicity are presented and defined in our work. CONCLUSIONS: Total area under the dose-volume profiles and specific cutoff points in low and intermediate dose levels have significant predictive potential toward the RT GI toxicity. In treatment planning, it seems that it is valuable to take into consideration the entire dose-volume primary distribution.

MRI-based preplanning using CT and MRI data fusion in patients with cervical cancer treated with 3D-based brachytherapy: feasibility and accuracy study.

PURPOSE: Magnetic resonance imaging (MRI)-assisted radiation treatment planning enables enhanced target contouring. The purpose of this study is to analyze the feasibility and accuracy of computed tomography (CT) and MRI data fusion for MRI-based treatment planning in an institution where an MRI scanner is not available in the radiotherapy department. METHODS AND MATERIALS: The registration inaccuracy of applicators and soft tissue was assessed in 42 applications with CT/MRI data fusion. The absolute positional difference of the center of the applicators was measured in four different planes from the top of the tandem to the cervix. Any inaccuracy of registration of soft tissue in relation to the position of applicators was determined and dose-volume parameters for MRI preplans and for CT/MRI fusion plans with or without target and organs at risk (OAR) adaptation were evaluated. RESULTS: We performed 6,132 measurements in 42 CT/MRI image fusions. Median absolute difference of the center of tandem on CT and MRI was 1.1 mm. Median distance between the center of the right ovoid on CT and MRI was 1.7 and 1.9 mm in the laterolateral and anteroposterior direction, respectively. Corresponding values for the left ovoid were 1.6 and 1.8 mm. Rotation of applicators was 3.1°. Median absolute difference in position of applicators in relation to soft tissue was 1.93, 1.50, 1.05, and 0.84 mm in the respective transverse planes, and 1.17, 1.28, 1.27, and 1.17 mm in selected angular directions. The dosimetric parameters for organs at risk on CT/MRI fusion plans without OAR adaptation were significantly impaired whereas the target coverage was not influenced. Planning without target adaptation led to overdosing of the target volume, especially high-risk clinical target volume--D90 88.2 vs. 83.1 (p < 0.05). CONCLUSIONS: MRI-based preplanning with consecutive CT/MRI data fusion can be safe and feasible, with an acceptable inaccuracy of soft tissue registration.

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.