Jaroslav Vanasek

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 radioterapy 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 ≥ 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 ≥ 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.ZusammenfassungZiel:Vergleich der Akut- und Spättoxizität nach dreidimensionaler konformaler Strahlentherapie der Prostata bis 74 Gy (3D-CRT) mit intensitätsmodulierter Radiotherapie bis 78 Gy (IMRT 78) und mit IMRT mit simultanem integrierten Boost bis 82 Gy (IMRT/ SIB 82).Patienten und Methodik:Die erste Gruppe bestand aus 94 Patienten, die eine 3D-CRT der Prostata und der Bläschendrüsenbasis bis 74 Gy erhielten. Die zweite Gruppe umfasste 138 Patienten, welche mit IMRT der Prostata und der Bläschendrüsenbasis bis 78 Gy behandelt wurden. Die letzte Gruppe erhielt eine IMRT mit SIB. Die verschriebenen Strahlendosen betrugen 82 Gy und 73,8 Gy in 42 Fraktionen auf die Prostata und die Bläschendrüsenbasis. Die Spättoxizität wurde anhand der RTOG/FC-LENT-Skala bewertet.Ergebnisse:Akute gastrointestinale Nebenwirkungen ≥ Grad 2 entwickelten 35,1% der Patienten mit 3D-CRT, 16% mit IMRT 78 und 7,7% mit IMRT/SIB 82. Akute urogenitale Nebenwirkungen ≥ Grad 2 traten bei 26,6% der Patienten mit 3D-CRT, 33% mit IMRT 78 und 30,7% mit IMRT/SIB 82 auf. Nach 3 Jahren betrug die geschätzte kumulative Inzidenz gastrointestinaler Spättoxizität Grad 3 14% für 3D-CRT, 5% für IMRT 78 und 2% für IMRT/SIB 82. Der Unterschied war signifikant (Log-Rank p = 0,02). Die geschätzte kumulative Inzidenz urogenitaler Spättoxizität Grad 3 lag bei 9% (3D-CRT), 7% (IMRT 78) und 6% (IMRT/ SIB 82) und zeigte keine Signifikanz (Log-Rank p = 0,32).Schlussfolgerung:Die Dosissteigerung auf 82 Gy mit SIB führt im Vergleich mit der 3D-CRT bis 74 Gy zu einer geringeren Rate an gastrointestinaler Spättoxizität Grad 3.

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.

Dose Escalation in Prostate Radiotherapy up to 82 Gy Using Simultaneous Integrated Boost

Purpose:To compare acute and late toxicity after three-dimensional conformal radiotherapy to the prostate to 74 Gy (3D-CRT) with intensity-modulated radioterapy 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 ≥ 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 ≥ 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.ZusammenfassungZiel:Vergleich der Akut- und Spättoxizität nach dreidimensionaler konformaler Strahlentherapie der Prostata bis 74 Gy (3D-CRT) mit intensitätsmodulierter Radiotherapie bis 78 Gy (IMRT 78) und mit IMRT mit simultanem integrierten Boost bis 82 Gy (IMRT/ SIB 82).Patienten und Methodik:Die erste Gruppe bestand aus 94 Patienten, die eine 3D-CRT der Prostata und der Bläschendrüsenbasis bis 74 Gy erhielten. Die zweite Gruppe umfasste 138 Patienten, welche mit IMRT der Prostata und der Bläschendrüsenbasis bis 78 Gy behandelt wurden. Die letzte Gruppe erhielt eine IMRT mit SIB. Die verschriebenen Strahlendosen betrugen 82 Gy und 73,8 Gy in 42 Fraktionen auf die Prostata und die Bläschendrüsenbasis. Die Spättoxizität wurde anhand der RTOG/FC-LENT-Skala bewertet.Ergebnisse:Akute gastrointestinale Nebenwirkungen ≥ Grad 2 entwickelten 35,1% der Patienten mit 3D-CRT, 16% mit IMRT 78 und 7,7% mit IMRT/SIB 82. Akute urogenitale Nebenwirkungen ≥ Grad 2 traten bei 26,6% der Patienten mit 3D-CRT, 33% mit IMRT 78 und 30,7% mit IMRT/SIB 82 auf. Nach 3 Jahren betrug die geschätzte kumulative Inzidenz gastrointestinaler Spättoxizität Grad 3 14% für 3D-CRT, 5% für IMRT 78 und 2% für IMRT/SIB 82. Der Unterschied war signifikant (Log-Rank p = 0,02). Die geschätzte kumulative Inzidenz urogenitaler Spättoxizität Grad 3 lag bei 9% (3D-CRT), 7% (IMRT 78) und 6% (IMRT/ SIB 82) und zeigte keine Signifikanz (Log-Rank p = 0,32).Schlussfolgerung:Die Dosissteigerung auf 82 Gy mit SIB führt im Vergleich mit der 3D-CRT bis 74 Gy zu einer geringeren Rate an gastrointestinaler Spättoxizität Grad 3.

Conformal Radiotherapy for Prostate Cancer&Longer Duration of Acute Genitourinary Toxicity in Patients with Prior History of Invasive Urological Procedure

The incidence and predictors of acute toxicity were evaluated in patients treated with three-dimensional conformal radiotherapy (3D-CRT) for localized prostate cancer. Between December 1997 and November 1999, 116 patients with T1-T3 prostatic carcinoma were enrolled in the study. Ninety patients were treated with 70 Gy and 26 patients with T3 tumors received 74 Gy. Of the 116 patients 42 (36.2%) had a prior history of invasive urological procedure (IUP) (transurethral resection of the prostate or transvesical prostatectomy for benign prostatic hyperplasia). Acute gastrointestinal (GI) and genitourinary (GU) symptoms were graded according to the EORTC/RTOG scoring system. Toxicity duration after the completion of 3D-CRT was recorded. The majority of patients experienced only mild or no (Grade 1) acute toxicities. Medications for GI and GU symptoms (Grade 2) were required by 28.4% and 12.9% of patients, respectively. Only one case of Grade 3 GI toxicity (0.9%) was observed. Seven patients (6.1%) experienced severe GU toxicity (Grade 3 or 4). No correlation was found between acute toxicity and age, stage, dose (70 Gy vs. 74 Gy), IUP and pelvic lymphadenectomy. A significant relationship was observed between the duration of acute GU toxicity and prior IUP. Symptoms persisted for more than 4 weeks in 51.9% and 26.0% of patients with and without a prior history of IUP, respectively (p = 0.02). The incidence of acute complications, associated with 3D-CRT for prostate cancer, was acceptable in our cohort of patients. A prior history of IUP resulted in a significantly longer duration of acute GU toxicity.The incidence and predictors of acute toxicity were evaluated in patients treated with three-dimensional conformal radiotherapy (3D-CRT) for localized prostate cancer. Between December 1997 and November 1999, 116 patients with T1-T3 prostatic carcinoma were enrolled in the study. Ninety patients were treated with 70 Gy and 26 patients with T3 tumors received 74 Gy. Of the 116 patients 42 (36.2%) had a prior history of invasive urological procedure (IUP) (transurethral resection of the prostate or transvesical prostatectomy for benign prostatic hyperplasia). Acute gastrointestinal (GI) and genitourinary (GU) symptoms were graded according to the EORTC/RTOG scoring system. Toxicity duration after the completion of 3D-CRT was recorded. The majority of patients experienced only mild or no (Grade 1) acute toxicities. Medications for GI and GU symptoms (Grade 2) were required by 28.4% and 12.9% of patients, respectively. Only one case of Grade 3 GI toxicity (0.9%) was observed. Seven patients (6.1%) experienced severe GU toxicity (Grade 3 or 4). No correlation was found between acute toxicity and age, stage, dose (70 Gy vs. 74 Gy), IUP and pelvic lymphadenectomy. A significant relationship was observed between the duration of acute GU toxicity and prior IUP. Symptoms persisted for more than 4 weeks in 51.9% and 26.0% of patients with and without a prior history of IUP, respectively (p = 0.02). The incidence of acute complications, associated with 3D-CRT for prostate cancer, was acceptable in our cohort of patients. A prior history of IUP resulted in a significantly longer duration of acute GU toxicity.

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.

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.

PET/CT significance for planning radiotherapy of head and neck cancer.

The combination of positron emission tomography and computed tomography (PET/CT) offers metabolic mapping in addition to anatomic information of the primary lesion, nodal and distant metastases in patients with head and neck tumors, and may be therefore beneficial for radiotherapy planning. The aim of our study was to evaluate benefits of combined PET and CT imaging for staging and target volume delineation in this group of patients.Fifty three patients (40 men and 13 women) with confirmed advanced, inoperable or non-radically operated head and neck cancer were assessed based on the results of PET/CT as well as standard diagnostic examinations. All patients were subsequently treated with intensity modulated radiotherapy (IMRT) with simultaneous integrated boost (SIB) of 6 MV X-rays. There was an agreement between the standard examinations results and results of PET/CT in 30 cases. In 23 cases there was disagreement either in tumor size, nodal involvement or presence of distant metastases. Results of the tumor size assessment differed significantly in 5 cases. There was no agreement found in nodal involvement in 10 cases. The cancer confirmed by standard examination was not found by PET/CT in 2 cases; 3 PET/CT positive findings were not confirmed by standard examinations. In 3 patients PET-CT revealed new distant metastatic disease. Based on PET/CT assessment we changed treatment strategy and applied potentially curative dose of radiotherapy to previously undiscovered regions in 9 patients. We decided to change the treatment intent in 3 cases and only palliative treatment was applied. Based on our experience and the literature review, PET/CT may be considerable contribution to the standard diagnostic procedures in approximately one third of cases.

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.

Perioperative interstitial CT-based brachytherapy boost in breast cancer patients with breast conservation after neoadjuvant chemotherapy.

Intraoperative placement of catheters in the tumor bed during breast-conserving surgery (BCS) enables postponed targeted boost irradiation in high risk breast cancer patients. Twenty-three patients with high risk breast cancer underwent neoadjuvant chemotherapy and multifractionated perioperative brachytherapy as a boost to the tumor bed using three-dimensional (3D) CT-based planning. Plastic catheters for brachytherapy were implanted during surgery and targeted irradiation was delivered in the course of 2-3 weeks. Acute and late toxicities were scored according to the RTOG Common Toxicity Criteria. Cosmetic outcomes were assessed using the Harvard criteria. No major perioperative complications were recorded. Circumscribed wound infection occurred in one patient (4.3%). Only 3 patients (13%) experienced acute skin toxicity Grade 1. We observed no teleangiectasias or pigmentations. The cosmetic outcome at last follow-up visit was rated as excellent/good, in 82.6%, fair, in 13% and poor in 4.4% of patients, respectively. There was no evidence of disease recurrence after median follow-up of 43. 4 months. Systematic integration of the perioperative fractionated 3D CT-based HDR brachytherapy as a boost for patients with breast cancer after BCS is feasible and seems safe. It might be beneficial especially for women with high risk of local recurrence.

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).