Bradley R. Pieters

Cardiac and lung complication probabilities after breast cancer irradiation

PURPOSE To assess for locoregional irradiation of breast cancer patients, the dependence of cardiac (cardiac mortality) and lung (radiation pneumonitis) complications on treatment technique and individual patient anatomy. MATERIALS AND METHODS Three-dimensional treatment planning was performed for 30 patients with left-sided breast cancer and various breast sizes. Two locoregional techniques (Techniques A and B) and a tangential field technique, including only the breast in the target volume, were planned and evaluated for each patient. In both locoregional techniques tangential photon fields were used to irradiate the breast. The internal mammary (IM)-medial supraclavicular (MS) lymph nodes were treated with an anterior mixed electron/photon field (Technique A) or with an obliquely incident mixed electron/photon IM field and an anterior electron/photon MS field (Technique B). The optimal IM and MS electron field dimensions and energies were chosen on the basis of the IM-MS lymph node target volume as delineated on CT-slices. The position of the tangential fields was adapted to match the IM-MS fields. Dose-volume histograms (DVHs) and normal tissue complication probabilities (NTCPs) for the heart and lung were compared for the three techniques. In the beams eye view of the medial tangential fields the maximum distance of the heart contour to the posterior field border was measured; this value was scored as the Maximum Heart Distance. RESULTS The lymph node target volume receiving more than 85% of the prescribed dose was on average 99% for both locoregional irradiation techniques. The breast PTV receiving more than 95% of the prescribed dose was generally smaller using Technique A (mean: 90%, range: 69-99%) than using Technique B (mean: 98%, range: 82-100%) or for the tangential field technique (mean: 98%, range: 91-100%). NTCP values for excess cardiac mortality due to acute myocardial ischemia varied considerably between patients, with minimum and maximum values of 0.1 and 7.5% (Technique A), 0.1 and 5.8% (Technique B) and 0.0 and 6.1% (tangential tech.). The NTCP values were on average significantly higher (P<0.001) by 1.7% (Technique A) and 1.0% (Technique B) when locoregional breast irradiation was given, compared with irradiation of the left breast only. The NTCP values for the tangential field technique could be estimated using the Maximum Heart Distance. NTCP values for radiation pneumonitis were very low for all techniques; between 0.0 and 1.0%. CONCLUSIONS Technique B results in a good coverage of the breast and locoregional lymph nodes, while Technique A sometimes results in an underdosage of part of the target volume. Both techniques result in a higher probability of heart complications compared with tangential irradiation of the breast only. Irradiation toxicity for the lung is low in all techniques. The Maximum Heart Distance is a simple and useful parameter to estimate the NTCP values for cardiac mortality for tangential breast irradiation.

Variability in target volume delineation on CT scans of the breast

PURPOSE To determine the intra- and interobserver variation in delineation of the target volume of breast tumors on computed tomography (CT) scans in order to perform conformal radiotherapy. MATERIALS AND METHODS The clinical target volume (CTV) of the breast was delineated in CT slices by four radiation oncologists on our clinically used delineation system. The palpable glandular breast tissue was marked with a lead wire on 6 patients before CT scanning, whereas 4 patients were scanned without a lead wire. The CTV was drawn by each observer on three separate occasions. Planning target volumes (PTVs) were constructed by expanding the CTV by 7 mm in each direction, except toward the skin. The deviation in the PTV extent from the average extent was quantified in each orthogonal direction for each patient to find a possible directional dependence in the observer variations. In addition, the standard deviation of the intra- and interobserver variation in the PTV volume was quantified. For each patient, the common volumes delineated by all observers and the smallest volume encompassing all PTVs were also calculated. RESULTS The patient-averaged deviations in PTV extent were larger in the posterior (42 mm), cranial (28 mm), and medial (24 mm) directions than in the anterior (6 mm), caudal (15 mm), and lateral (8 mm) directions. The mean intraobserver variation in volume percentage (5.5%, 1 SD) was much smaller than the interobserver variation (17.5%, 1 SD). The average ratio between the common and encompassing volume for the four observers separately was 0.82, 0.74, 0.82, and 0.80. A much lower combined average ratio of 0.43 was found because of the large interobserver variations. For the observer who placed the lead wire, the intraobserver variation in volume was decreased by a factor of 4 on scans made with a lead wire in comparison to scans made without a lead wire. For the other observers, no improvement was seen. Based on these results, an improved delineation protocol was designed. CONCLUSIONS Intra- and especially interobserver variation in the delineation of breast target volume on CT scans can be rather large. A detailed delineation protocol making use of CT scans with lead wires placed on the skin around the palpable breast by the delineating observer reduces the intraobserver variation. To reduce the interobserver variation, better imaging techniques and pathology studies relating glandular breast tissue to imaging may be needed to provide more information on the extent of the clinical target volume.

Comparison of three radiotherapy modalities on biochemical control and overall survival for the treatment of prostate cancer: A systematic review

BACKGROUND AND PURPOSE For the radiation treatment of prostate cancer high dose should be delivered for optimal biochemical control. Treatment can be given by dose-escalated external beam radiotherapy (EBRT) or external beam radiotherapy combined with a radioactive seed implantation (EBSeeds) or high-dose rate (HDR) brachytherapy (EBTI). Differences in outcome between the modalities were assessed by a systematic review. MATERIALS AND METHODS A systematic search was performed resulting in 40 articles to be used. Data were extracted on biochemical control and overall survival at 3, 5, and 8 years and other time points mentioned in the articles. Also known prognostic parameters were noted. Comparison of the modalities was done by a Weibull survival analysis and estimation of Hazard Ratios (HR) was done with 95% confidence intervals (95% CIs). RESULTS The HR for biochemical recurrence was 1.40 (95% CI 1.31-1.51) for EBRT relative to EBTI, and was 1.37 (95% CI 1.26-1.49) for EBSeeds relative to EBTI. The HR for overall survival was 1.50 (95% CI 1.29-1.73) for EBRT relative to EBTI, and was 2.33 (95% CI 2.04-2.66) for EBSeeds relative to EBTI. CONCLUSION The combination of external beam radiotherapy and HDR brachytherapy results in a superior biochemical control and overall survival found in a systematic review on radiotherapy for prostate cancer.

AN IMPROVED TECHNIQUE FOR BREAST CANCER IRRADIATION INCLUDING THE LOCOREGIONAL LYMPH NODES

PURPOSE To find an irradiation technique for locoregional irradiation of breast cancer patients which, compared with a standard technique, improves the dose distribution to the internal mammary-medial supraclavicular (IM-MS) lymph nodes. The improved technique is intended to minimize the lung dose and reduce the dose to the heart. METHODS AND MATERIALS The standard technique consists of an anterior mixed electron/photon IM-MS field. In the improved technique, an oblique electron and an oblique asymmetric photon field are combined to irradiate the IM lymph nodes. To irradiate the MS lymph nodes, a combination of an anterior electron and an anterior asymmetric photon field is used. For both the standard and the improved technique, tangential photon fields are used to irradiate the breast. Three-dimensional (3D) treatment planning was performed for 8 patients with various breast sizes for these two techniques. Dose-volume histograms (DVHs) and normal tissue complication probabilities (NTCPs) were compared for both techniques. The field dimensions and energy of the standard technique were determined at simulation, whereas for the improved technique the fields were designed by CT-based treatment planning. RESULTS The dose in the breast planning target volume was essentially the same for both techniques. For the improved technique, combined with 3D localization information, an improvement in the IM-MS planning target coverage is seen. The volume within the 95% isodose surface was on average 25% (range, 0-64%) and 74% (range, 43-90%) for the standard and improved technique, respectively. The heart generally receives less dose with the improved technique. However, sometimes a small but acceptable increase in lung dose is found. CONCLUSION The improved technique, combined with localization information of the IM-MS lymph nodes, greatly improves the dose distribution in the planning target volume for a large group of patients without significantly increasing the dose to organs at risk.

Short Androgen Suppression and Radiation Dose Escalation for Intermediate- and High-Risk Localized Prostate Cancer: Results of EORTC Trial 22991

PURPOSE Up to 30% of patients who undergo radiation for intermediate- or high-risk localized prostate cancer relapse biochemically within 5 years. We assessed if biochemical disease-free survival (DFS) is improved by adding 6 months of androgen suppression (AS; two injections of every-3-months depot of luteinizing hormone-releasing hormone agonist) to primary radiotherapy (RT) for intermediate- or high-risk localized prostate cancer. PATIENTS AND METHODS A total of 819 patients staged: (1) cT1b-c, with prostate-specific antigen (PSA) ≥ 10 ng/mL or Gleason ≥ 7, or (2) cT2a (International Union Against Cancer TNM 1997), with no involvement of pelvic lymph nodes and no clinical evidence of metastatic spread, with PSA ≤ 50 ng/mL, were centrally randomized 1:1 to either RT or RT plus AS started on day 1 of RT. Centers opted for one dose (70, 74, or 78 Gy). Biochemical DFS, the primary end point, was defined from entry until PSA relapse (Phoenix criteria) and clinical relapse by imaging or death of any cause. The trial had 80% power to detect hazard ratio (HR), 0.714 by intent-to-treat analysis stratified by dose of RT at the two-sided α = 5%. RESULTS The median patient age was 70 years. Among patients, 74.8% were intermediate risk and 24.8% were high risk. In the RT arm, 407 of 409 patients received RT; in the RT plus AS arm, 403 patients received RT plus AS and three patients received RT only. At 7.2 years median follow-up, RT plus AS significantly improved biochemical DFS (HR, 0.52; 95% CI, 0.41 to 0.66; P < .001, with 319 events), as well as clinical progression-free survival (205 events, HR, 0.63; 95% CI, 0.48 to 0.84; P = .001). In exploratory analysis, no statistically significant interaction between treatment effect and dose of RT could be evidenced (heterogeneity P = .79 and P = .66, for biochemical DFS and progression-free survival, respectively). Overall survival data are not mature yet. CONCLUSION Six months of concomitant and adjuvant AS improves biochemical and clinical DFS of intermediate- and high-risk cT1b-c to cT2a (with no involvement of pelvic lymph nodes and no clinical evidence of metastatic spread) prostatic carcinoma, treated by radiation.

Comparison of biologically equivalent dose–volume parameters for the treatment of prostate cancer with concomitant boost IMRT versus IMRT combined with brachytherapy

BACKGROUND AND PURPOSE The two main modalities to deliver high dose to the prostate and prevent high doses to neighboring organs are intensity modulated radiotherapy (IMRT) or external beam radiotherapy combined with brachytherapy. Because of the different biological effectiveness the physical dose distributions were converted to 3-dimensional linear quadratic dose at 2 Gy per fraction (EQD(2)). From the latter, cumulative EQD(2)-volume histograms were determined for comparison of the modalities. MATERIAL AND METHODS An IMRT plan was made on the contoured planning target volume (PTV1) and organs at risk (OAR) of 20 patients (IMRT-only). A dose of 70 Gy was prescribed on the PTV1 with a concomitant boost to a total of 76 Gy on a subvolume (PTV2). Also a 46 Gy IMRT plan was made combined with either a pulsed dose-rate (PDR) or a high dose-rate (HDR) brachytherapy boost. The EQD(2) on the PTV1 of the combined IMRT-PDR and IMRT-HDR plans were made equivalent to the EQD(2) of the 70 Gy IMRT-only plan. The alpha/beta-ratio for prostate was set to 1.5 Gy and 10 Gy. For normal tissues an alpha/beta-ratio of 3.0 Gy was taken. Several EQD(2)-volume histogram parameters were calculated for comparison and analyzed by two-way ANOVA. RESULTS The mean EQD(2) to 95% of the prostate volume was slightly higher for the IMRT-only plan than for the brachytherapy modalities (P<0.001), in contrast to the mean EQD(2) to 50% of the prostate volume in which the opposite was the case (P<0.001). Rectum and bladder doses for IMRT-only are significantly higher (P<0.001). The urethra dose for IMRT-HDR was much higher than the other modalities only when the alpha/beta-ratio for prostate was 10 Gy. CONCLUSION Because of the high doses within an implant, the dose in 50% of the prostate volume is much higher with the brachytherapy modalities than IMRT-only which may have clinical consequences. With brachytherapy the doses to the OAR are lower or similar to IMRT-only. Dose escalation for prostate tumors is more easily achieved with brachytherapy than with IMRT alone. Therefore, brachytherapy might be the preferred modality to achieve further dose escalation.

Imaging findings in craniofacial childhood rhabdomyosarcoma

Rhabdomyosarcoma (RMS) is the commonest paediatric soft-tissue sarcoma constituting 3–5% of all malignancies in childhood. RMS has a predilection for the head and neck area and tumours in this location account for 40% of all childhood RMS cases. In this review we address the clinical and imaging presentations of craniofacial RMS, discuss the most appropriate imaging techniques, present characteristic imaging features and offer an overview of differential diagnostic considerations. Post-treatment changes will be briefly addressed.

The AMORE Protocol for Advanced-Stage and Recurrent Nonorbital Rhabdomyosarcoma in the Head-and-Neck Region of Children: A Radiation Oncology View

PURPOSE A multidisciplinary approach, consisting of consecutive Ablative Surgery, MOld technique with afterloading brachytherapy and immediate surgical REconstruction (AMORE) applied after chemotherapy, was designed for children with rhabdomyosarcoma in the head-and-neck region. Analysis of the first 42 patients was performed. METHODS AND MATERIALS After macroscopically radical tumor resection, molds were constructed for each individual to fit into the surgical defect. The molds, made of 5-mm-thick layers of thermoplastic rubber, consisted of different parts. Flexible catheters were positioned between layers. After brachytherapy, the molds were removed. Surgical reconstruction was performed during the same procedure. RESULTS Dose to the clinical target volume varied from 40 to 50 Gy for the primary treatment (31 patients) and salvage treatment groups (11 patients). There were 18 females and 24 males treated from 1993 until 2007. Twenty-nine tumors were located in the parameningeal region, and 13 were located in the nonparameningeal region. Patient age at the time of AMORE was 1.2-16.9 years (average, 6.5 years). Follow-up was 0.2-14.5 years (average, >5.5 years). Eleven patients died, 3 with local recurrence only, 6 with local and distant disease, 1 died of distant metastases only, and 1 patient died of a second primary tumor. Overall 5-year survival rates were 70% for the primary treatment group and 82% for the salvage group. Treatment was well tolerated, and acute and late toxicity were mild. CONCLUSIONS The AMORE protocol yields good local control and overall survival rates, and side effects are acceptable.

Standardization of definitions in focal therapy of prostate cancer: report from a Delphi consensus project

PurposeTo reach standardized terminology in focal therapy (FT) for prostate cancer (PCa).MethodsA four-stage modified Delphi consensus project was undertaken among a panel of international experts in the field of FT for PCa. Data on terminology in FT was collected from the panel by three rounds of online questionnaires. During a face-to-face meeting on June 21, 2015, attended by 38 experts, all data from the online rounds were reviewed and recommendations for definitions were formulated.ResultsConsensus was attained on 23 of 27 topics; TargetedFT was defined as a lesion-based treatment strategy, treating all identified significant cancer foci; FT was generically defined as an anatomy-based (zonal) treatment strategy. Treatment failure due to the ablative energy inadequately destroying treated tissue is defined as ablation failure. In targeting failure the energy is not adequately applied to the tumor spatially and selection failure occurs when a patient was wrongfully selected for FT. No definition of biochemical recurrence can be recommended based on the current data. Important definitions for outcome measures are potency (minimum IIEF-5 score of 21), incontinence (new need for pads or leakage) and deterioration in urinary function (increase in IPSS >5 points). No agreement on the best quality of life tool was established, but UCLA-EPIC and EORTC-QLQ-30 were most commonly supported by the experts. A complete overview of statements is presented in the text.ConclusionFocal therapy is an emerging field of PCa therapeutics. Standardization of definitions helps to create comparable research results and facilitate clear communication in clinical practice.

Clinical Results of a Concomitant Boost Radiotherapy Technique for Muscle-Invasive Bladder Cancer

Purpose:To update the results of external radiotherapy with a focal concomitant boost technique on local control and bladder function in patients with muscle-invasive bladder cancer.Patients and Methods:The authors retrospectively evaluated 92 elderly or disabled patients with localized T2–4 N0–1 M0 transitional cell carcinoma of the bladder and a median age of 79 years, not suitable for radical surgery and treated between 1994 and 2005. Treatment consisted of a dose of 40 Gy/2 Gy to the small pelvis with a daily concomitant boost of 0.75 Gy to the tumor. Total dose was 55 Gy in 4 weeks.Results:Complete remission rate after evaluation by means of cystoscopy at 3 months was 78%. 3-year local control rate amounted to 56%, and 3-year overall survival to 36%. The posttreatment bladder capacity was comparable with the pretreatment capacity and was ≥ 200 ml in 81% of the cases. Mean bladder capacity did not deteriorate at longer follow-up.Conclusion:The local control rate after external beam radiotherapy in elderly patients with a focal concomitant boost for localized muscle-invasive bladder cancer was 56% at 3 years. Functional bladder outcome was good.Ziel:Analyse der Ergebnisse einer primären perkutanen Strahlentherapie mit konkomitanter Boost-Technik hinsichtlich lokaler Tumorkontrolle und Blasenfunktion.Patienten und Methodik:Retrospektive Analyse der lokalen Tumorkontrolle, des Gesamtüberlebens und der Blasenfunktion von 92 Patienten mit lokal fortgeschrittenem, nicht metastasiertem, muskelinvasivem Harnblasenkarzinom (T2–T4 N0–1 M0). Der Altersdurchschnitt betrug 79 Jahre, eine Radikaloperation war aus funktionellen Gründen nicht möglich. Die Strahlentherapie erfolgte im Zeitraum von 1994 bis 2005. Die Dosisverschreibung betrug 40 Gy/2 Gy perkutan auf das kleine Becken, zusätzlich wurde ein tumorfokussierter Boost mit täglich 0,75 Gy appliziert. Die kumulative Dosis betrug 55 Gy in 4 Wochen.Ergebnisse:Zystoskopisch zeigte sich bei 78% der Patienten nach 3 Monaten eine komplette Remission. Nach 3 Jahren waren noch 56% der Patienten tumorfrei. Das 3-Jahres-Überleben betrug 36%. Während der gesamten Nachbeobachtungszeit kam es zu keiner Verschlechterung der funktionellen Blasenkapazität, die bei 81% der Patienten ≥ 200 ml betrug.Schlussfolgerung:Die perkutane Strahlentherapie mit gleichzeitigem fokussiertem Boost führte beim muskelinvasiven Blasenkarzinom in 56% zu einer mehrjährigen lokalen Tumorkontrolle bei gleichbleibend guter Blasenfunktion.