Martin Dolezel

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.

Liposomal doxorubicin combined with regional hyperthermia: Reducing systemic toxicity and improving locoregional efficacy in the treatment of solid tumors

Summary Incorporation of doxorubicin into polyethylene glycol-coated (pegylated) liposomes increases the therapeutic index, prolongs circulation time and enhances tumor localization. Pegylated liposomal doxorubicin (PLD) is an established therapeutic agent in epithelial ovarian carcinoma (EOC), breast carcinoma or Kaposi’s sarcoma, and PLD administration results in reduction of toxicity. Addition of regional hyperthermia increases liposome extravasation, induces the doxorubicin release from the liposomes, and the combination of hyperthermia and doxorubicin itself may be supra-additive, resulting in enhanced antitumor efficacy in the heated region. Encouraging results have been reported for the combination of PLD and hyperthermia in EOC, breast carcinoma and hepatocellular carcinoma.

Magnetic Resonance Imaging in Postprostatectomy Radiotherapy Planning

PURPOSE To investigate whether the use of magnetic resonance imaging (MRI) in prostate bed treatment planning could influence definition of the clinical target volume (CTV) and organs at risk. METHODS AND MATERIALS A total of 21 consecutive patients referred for prostate bed radiotherapy were included in the present retrospective study. The CTV was delineated according to the European Organization for Research and Treatment of Cancer recommendations on computed tomography (CT) and T(1)-weighted (T(1)w) and T(2)-weighted (T(2)w) MRI. The CTV magnitude, agreement, and spatial differences were evaluated on the planning CT scan after registration with the MRI scans. RESULTS The CTV was significantly reduced on the T(1)w and T(2)w MRI scans (13% and 9%, respectively) compared with the CT scans. The urinary bladder was drawn smaller on the CT scans and the rectum was smaller on the MRI scans. On T(1)w MRI, the rectum and urinary bladder were delineated larger than on T(2)w MRI. Minimal agreement was observed between the CT and T(2)w images. The main spatial differences were measured in the superior and superolateral directions in which the CTV on the MRI scans was 1.8-2.9 mm smaller. In the posterior and inferior border, no difference was seen between the CT and T(1)w MRI scans. On the T(2)w MRI scans, the CTV was larger in these directions (by 1.3 and 1.7 mm, respectively). CONCLUSIONS The use of MRI in postprostatectomy radiotherapy planning resulted in a reduction of the CTV. The main differences were found in the superior part of the prostate bed. We believe T(2)w MRI enables more precise definition of prostate bed CTV than conventional planning CT.

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 ≤ 55 years (p < 0.001), pre-radiotherapy hemoglobin (Hb) level > 12 g/dl (p = 0.009), and pre-radiotherapy dose of dexamethasone ≤ 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.Ziel:Evaluation prognostischer Faktoren bei Patienten mit Glioblastom, die mit postoperativer oder primärer Strahlentherapie behandelt wurden.Patienten und Methodik:Bei 100 Patienten mit Glioblastom wurde in den Jahren 1989–2000 die Strahlentherapie im Rahmen der Primärbehandlung angewandt. Bei allen Patienten wurde eine Operation oder Biopsie mit nachfolgender konventioneller perkutaner Bestrahlung durchgeführt. Der Einfluss der prognostischen Faktoren wurde bei 85 Patienten, die die geplante Strahlendosis (60 Gy in 30 Fraktionen) erhielten, evaluiert. 73/85 Patienten (86%) wurden mit postoperativer Bestrahlung, 12/85 Patienten (14%) mit primärer Strahlentherapie und Biopsie behandelt.Ergebnisse:Die mittlere Überlebenszeit betrug 10,1 (3,7–49,8) Monate, die Überlebenszeit nach 1 und 2 Jahren lag bei 41% bzw. 5%. Mittels der univariaten Analyse stellten sich folgende Faktoren dar, die mit einer längeren Überlebenszeit verbunden sind: ein Alter ≤ 55 Jahre (p < 0,001), eine Hämoglobin-(Hb-)Konzentration zu Beginn der Strahlentherapie > 12 g/dl (p = 0,009) und eine prätherapeutische Dexamethasondosis ≤ 2 mg/Tag (p = 0,005). Die multivariate Analyse ermittelte ein jüngeres Alter (p < 0,001), eine höhere Hb-Konzentration (p = 0,002), eine niedrigere Dexamethasondosis (p = 0,026) und eine hemisphärische Tumorlokalisation (p = 0.019) als unabhängige prognostische Faktoren für eine längere Überlebenszeit. Die mittlere Überlebenszeit bei Patienten mit einer Hb-Konzentration > 12 g/dl betrug 12,1 Monate, bei Patienten mit einem niedrigeren Blut-Hb-Wert dagegen nur 7,9 Monate. Die Kontingenztabellenstatistik zeigte keine signifikanten Unterschiede in der Distribution der anderen prognostischen Faktoren bei beiden Hb-Gruppen.Schlussfolgerung:Die Ergebnisse weisen darauf hin, dass eine niedrigere Hb-Konzentration vor Beginn der Strahlentherapie wegen Glioblastoms einen negativen Einfluss auf die Prognose haben kann. Diese Beobachtung verdient weitere Aufmerksamkeit.

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.

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.

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.

Outcomes of adrenalectomy in patients with primary hyperaldosteronism - a single centre experience

INTRODUCTION Primary hyperaldosteronism is a common cause of secondary hypertension. In patients with proven unilateral overproduction of aldosterone adrenalectomy can cure hyperaldosteronism with high probability and a positive effect on hypertension. The aim of the study was to determine the effects of unilateral adrenalectomy on blood pressure and laboratory parameters. The secondary objective was to identify parameters that would allow the prediction of hypertension cure. METHODS We performed a cross-sectional analysis of the data of patients who underwent unilateral adrenalectomy for primary aldosteronism at the Department of Urology of University Hospital Olomouc in the years 2000-2011. We assesed the preoperative clinical conditions of patients, the results of biochemical and radiological examinations, course of the surgery and post-operative course including laboratory and clinical parameters during the 12 months postoperatively. RESULTS 62 patients underwent adrenalectomy for primary aldosteronism in this period. Four patients were excluded from the study due to surprising histology (myelolipoma in 2, carcinoma in 2), seven patients had incomplete postoperative data. The statistical analysis therefore included 51 patients, of which 57% were females. CT or MRI was performed in all patients; 63% patients underwent superselective catheterization of adrenal veins (AVS). Adrenalectomy was performed in all cases laparoscopically. Histology most often showed adrenal hyperplasia (59%), adenoma was detected in 37% and adenoma on the basis of micronodular hyperplasia in 4%. Twelve months after surgery the antihypertensive drugs were discontinued in 17/51 (33%) and the number or dose of antihypertensive drugs was reduced in 25/51 (49%). Normokalemia and normalisation of the aldosterone-renin ratio (ARR) was detected in 92% and 84% of the patients. Performing AVS did not statistically significantly influence the rate of blood pressure control or normalization of ARR, which is probably due to small study size. This study demonstrated a better effect of surgery on blood pressure in younger patients. CONCLUSIONS Unilateral adrenalectomy had a positive effect in 82% of the patients operated for primary aldosteronism and lead to either blood pressure normalization or reduction of the antihypertensive medication.

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.