Petr Paluska

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.

High-dose rate brachytherapy in the treatment of penile carcinoma--first experience.

PURPOSE Interstitial low-dose rate brachytherapy (BRT) allows a conservative treatment of T1-T2 penile carcinoma. High-dose rate (HDR) BRT is often considered as a dangerous method for interstitial implants because of higher risk of complications. However, numerous reports suggest that results of HDR-BRT may be comparable to low-dose rate BRT. There are no data available in the literature regarding HDR interstitial BRT for carcinoma of the penis. METHODS AND MATERIALS Ten patients with early penile carcinoma were treated by interstitial hyperfractionated HDR-BRT at the dose of 18 times 3Gy twice daily between years 2002 and 2009. Breast interstitial BRT template was used for fixation and precise geometry reconstruction of stainless hollow needles. RESULTS Median followup was 20 months. Our BRT technique and fractionation schedule was well tolerated by all patients. Acute reaction consisted predominantly of penis edema and Grade 2 radiation mucositis that dissolved during 8 weeks after the treatment. We neither observed any postradiation necrosis nor urethral stenosis. The worst late side effects recorded were mild telanagiectasias in the treatment region. At the last followup, all patients were alive without evidence of the tumor and with fully functional organ. CONCLUSIONS Hyperfractionated interstitial HDR-BRT with 18 times 3 Gy per fraction twice daily is a promising method in selected patients of penile carcinoma and deserves further evaluation in a larger prospective study.

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.

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.

Utilization of cone‐beam CT for reconstruction of dose distribution delivered in image‐guided radiotherapy of prostate carcinoma — bony landmark setup compared to fiducial markers setup

The purpose of this study was to compare two different styles of prostate IGRT: bony landmark (BL) setup vs. fiducial markers (FM) setup. Twenty‐nine prostate patients were treated with daily BL setup and 30 patients with daily FM setup. Delivered dose distribution was reconstructed on cone‐beam CT (CBCT) acquired once a week immediately after the alignment. Target dose coverage was evaluated by the proportion of the CTV encompassed by the 95% isodose. Original plans employed 1 cm safety margin. Alternative plans assuming smaller 7 mm margin between CTV and PTV were evaluated in the same way. Rectal and bladder volumes were compared with initial ones. While the margin reduction in case of BL setup makes the prostate coverage significantly worse (p=0.0003, McNemars test), in case of FM setup with the reduced 7 mm margin, the prostate coverage is even better compared to BL setup with 10 mm margin (p=0.049, Fishers exact test). Moreover, partial volumes of organs at risk irradiated with a specific dose can be significantly lowered (p<0.0001, unpaired t‐test). Reducing of safety margin is not acceptable in case of BL setup, while the margin can be lowered from 10 mm to 7 mm in case of FM setup. PACS numbers: 87.55.dk, 87.55.km, 87.55.tm

Quantitative evaluation of the benefit of fiducial image-guidance for prostate cancer intensity modulated radiation therapy using daily dose volume histogram analysis.

To quantitatively evaluate the extent to which fiducial-based image-guidance improves dose coverage of the target volume and sparing of critical organs for prostate cancer patients treated with intensity modulated radiotherapy (IMRT) and determination of planning margins by original approach of detailed daily dose volume histogram (DVH) and patients position correction analysis. Sixty-two patients divided in two groups (clinical target volume (CTV) → planning target volume (PTV) margin 10 and 7 mm) were treated with IMRT using implanted fiducial markers. Each patients treatment fraction was recalculated as it would have been treated without fiducial-guided positioning. For both plans (IGRT and non-IGRT), equivalent uniform doses (EUD), maximal and minimal doses for target volumes, normal tissue complication probability (NTCP), maximum and mean doses for organs at risk and the whole DVH differences were assessed. In the group with 10 mm margins, the only significant difference was worse rectal NTCP by 4.5%, but the CTV dose coverage remained at the same level. Recalculated plans with 7 mm margin could not achieve the prescribed target volume coverage, and the EUD decreased by 3.7 and 0.6 Gy for PTV and CTV, respectively. Desired CTV → PTV margin for non-IGRT plans should be no lower than 12 mm to guarantee 95% instances when delivered dose to CTV maintain as planned, for IGRT plans decrease this requirement to 2 mm. Prostate IMRT strategies involving margin reduction below 7 mm require image-guidance to maintain the planned dose coverage. Using fiducial-based image-guidance and large margins seems to be superfluous.

IMRT using simultaneous integrated boost (66 Gy in 6 weeks) with and without concurrent chemotherapy in head and neck cancer – toxicity evaluation

Summary Aim To evaluate the toxicity of intensity-modulated radiotherapy with simultaneous integrated boost (SIB-IMRT) in head and neck cancer patients treated using a protocol comprising 66 Gy to the PTV1 (planning target volume; region of macroscopic tumour) and 60 Gy and 54 Gy to the regions with high risk (PTV2) and low risk (PTV3) of subclinical disease in 30 fractions in six weeks. Material and Methods Between December 2003 and February 2006, 48 patients (median age 55; range 25–83, performance status 0–1) with evaluable non-metastatic head and neck cancer of various localizations and stages (stages: I–1; II–8; III–12; IV–27 patients, resp.) were irradiated according to the protocol and followed (median follow-up 20 months; range 4–42). Ten patients underwent concurrent chemotherapy (CT) and in 15 patients the regimen was indicated postoperatively because of close or positive margins. In all cases the regimen was used as an alternative to conventional radiotherapy (70 Gy in 7 weeks). The acute and late toxicities were evaluated according to RTOG and RTOG/EORTC toxicity scales, respectively. Results All patients finished the treatment without the need for interruption due to acute toxicity. No patient experienced grade 4 toxicity. More severe acute toxicity was observed in patients with CT, but the most severe toxicity was grade 3. Grade 3 toxicity was observed in the skin, mucous membrane, salivary glands, pharynx/oesophagus and larynx in 8.4%, 35.4%, 39.6% and 2.1%, in the CT subgroup in 10%, 100%, 90%, 10%, respectively. The trend of impairment of acute toxicity by concurrent chemotherapy was statistically confirmed by Fishers exact test (for mucous membranes p=0.000002 and pharyngeal/oesophageal toxicity p=0.0004). The most severe late toxicity was grade 2 subcutaneous tissue (34.2%), mucous membrane (36.8%) and larynx (11.1%), grade 3 in salivary gland (2.6%) and grade 1 in skin (84.2%) and spinal cord (5.4%). The late toxicity was not increased by chemotherapy. Conclusion In light of the toxicity profile we consider the presented regimen to be an alternative to conventional radiotherapy 70 Gy in 7 weeks. The addition of CT requires more intensive supportive care.

Daily prostate volume anD position monitoring using implanteD golD markers anD on-boarD imaging During raDiotherapy

PURPOSE This study aimed to evaluate prostate volume changes and prostate motions during radiotherapy. METHODS In 2010, twenty-five patients were treated for prostate cancer by external beam radiotherapy with implanted fiducial markers. Coordinates of three gold markers on kilovoltage images were calculated daily. Volume changes in target structure were observed through changes in intermarker distances. Differences in patient position between laser-tattoo alignment and gold marker localization were evaluated. Intrafraction motion was assessed by measuring marker displacement on kilovoltage images acquired before and after fraction delivery. RESULTS Prostate shrinkage was observed in 60% of patients. The average shrinkage was 7% of the prostates initial volume. Corrections after laser-tattoo alignment remained mostly below 1 cm. The difference between marker centroid position on the actual images and the planning images was 2 +/- 1 mm on average. The extension of intrafraction movements was 7.6 +/- 0.2 mm on average. CONCLUSIONS In our retrospective study, the possibility for prostate volume changes during radiotherapy was revealed. Intrafraction movements turned out to be the limiting factor in safety margin reduction.

Predicting factors for locoregional failure of high-dose-rate brachytherapy for early-stage oral cancer

AIM Brachytherapy is an alternative to surgery in the treatment of the early stages of oral tongue cancer. The aim of this retrospective study was to analyze the clinical risk factors and possible candidate biomarkers of local and regional tumor control. PATIENTS & METHODS Twenty-four patients were treated between the years 2001 and 2010. Median follow-up was 37.4 months. Correlation between disease-free survival and clinical stage, tumor grade, resection margin, depth of invasion, and p16, EGF receptor, NF-κB, HIF-1α, HER2, Ku-80, COX-2 and VEGF expression was evaluated. RESULTS The estimated 5-year local control was 81% and locoregional control was 62%. Depth of tumor invasion (p = 0.018) and higher VEGF expression (p = 0.016) were significantly predictive for worse disease-free survival in Cox multivariate analysis. CONCLUSION Intensity of VEGF expression and depth of tumor invasion may be significantly negative predictors of disease-free survival in tongue cancer patients treated by brachytherapy alone. Predictive value of VEGF deserves evaluation in larger studies.