Risk-adapted moderate hypofractionation of prostate cancer : A prospective analysis of acute toxicity, QOL and outcome in 221 patients.

PURPOSE: Prostate cancer (PCA) is highly heterogeneous in terms of its oncologic outcome. We therefore aimed to tailor radiation treatment to the risk status by using three different hypofractionated radiation regimen differing in applied dose, use of rectum spacer, inclusion of pelvic lymph nodes (pLN) and use of androgen deprivation therapy (ADT). Here we report on acute toxicity, quality of life (QOL) and oncologic outcome at a median follow-up of 12 months. METHODS: A total of 221 consecutive PCA patients received hypofractionated intensity-modulated radiotherapy (IMRT). Low-risk (LR) patients were planned to receive 60 Gy in 20 fractions (EQD2α/ß1.5 = 77.1 Gy), intermediate-risk (IR) patients 63 Gy in 21 fractions (EQD2α/ß1.5 = 81 Gy), and high-risk (HR) patients 67.5 Gy in 25 fractions (EQD2α/ß1.5 = 81 Gy) to the prostate and 50 Gy in 25 fractions to the pLN. Acute rectal toxicity was assessed by endoscopy. In addition, toxicity was scored using CTC-AE 4.0 and IPSS score, while QOL was assessed using QLQ-PR25 questionnaires. RESULTS: Acute CTC reactions were slightly higher in the HR regimen but reverted to baseline at 3 months. GI G2 toxicity was 4%, 0% and 12% for the LR, IR and HR regimen. Compared to IR patients, the increase in toxicity in HR patients was statistically significant (p = 0.002) and mainly caused by a higher incidence of diarrhea presumably due to pelvic EBRT. QOL scores of all domains were worse for the HR regimen (not significant). CONCLUSION: Risk-adapted moderate hypofractionation is associated with low GI/GU toxicity. Given the higher rate of pelvic metastases in HR patients, slightly higher transient acute reactions should be outweighed by possible oncological benefits.

Mesonephric adenocarcinoma of the vagina : Diagnosis and multimodal treatment of a rare tumor and analysis of worldwide experience.

BACKGROUND: Mesonephric adenocarcinoma of the vagina is an extremely rare tumor of the female genital tract, with only a few cases reported so far worldwide. Consequently, there is no established standard treatment and limited knowledge about the prognosis and biologic behavior of vaginal mesonephric adenocarcinoma. METHODS: This report documents a new case of vaginal mesonephric adenocarcinoma diagnosed in a 54-year-old woman, and analyzes this in the context of all previously published cases. RESULTS: MRI demonstrated that the 2.5 × 1.8 cm tumor of the vaginal wall was invading urethra and bladder. Following surgical excision, histologic analysis determined mesonephric adenocarcinoma of the vagina, stage pT2 R1. In order to avoid the mutilating extended surgery which would be required to reach R0 and considerable impairment of quality of life, adjuvant radiochemotherapy was administered with external radiation and brachytherapy, including 5 cycles of cisplatin (40 mg/m²) for radiosensitization. After 4 years of continuous oncologic follow-up, the patient is alive and clinically free of disease. CONCLUSION: In this case it was shown that adjuvant radiochemotherapy with radiation and brachytherapy was effective to manage the surgical R1 situation and maintain the patient's life quality. More published cases reports are needed to gradually substantiate optimal treatment strategies.

Comparison of two different rectal spacers in prostate cancer external beam radiotherapy in terms of rectal sparing and volume consistency.

BACKGROUND AND PURPOSE: In external beam radiation (EBRT) of the prostate, the rectum is the dose-limiting organ at risk, and sparing of the anterior rectal wall is a prerequisite for safe delivery of doses beyond 70 Gy. Spatial sparing of the rectum can be achieved by introducing a spacer material into the retroprostatic space, thus separating the anterior rectal wall from the PTV. MATERIALS AND METHODS: Two spacer technologies, Spacer OAR, a polyethylene glycol gel and ProSpace, a saline inflated balloon, were compared in terms of spacer volume, stability, and dose reduction to the anterior rectum wall in 78 patients. RESULTS: Both spacer systems significantly reduced the rectum surface encompassed by the 95% isodose (gel: -35%, p<0.01; balloon -63.4%, p<0.001) compared to a control group. The balloon spacer was superior in reducing rectum dose (-27.7%, p=0.034), but exhibited an average volume loss of >50% during the full course of treatment of 37-40 fractions, while the volume of gel spacers remained fairly constant. CONCLUSIONS: In choosing between the two spacer technologies, the advantageous dose reduction of the balloon needs to be weighed up against the better volume consistency of the gel spacer with respect to the duration of hypofractionated vs normofractionated regimens.

First clinical release of an online, adaptive, aperture-based image-guided radiotherapy strategy in intensity-modulated radiotherapy to correct for inter- and intrafractional rotations of the prostate.

PURPOSE: We developed and evaluated a correction strategy for prostate rotations using direct adaptation of segments in intensity-modulated radiotherapy (IMRT). METHOD AND MATERIALS: Implanted fiducials (four gold markers) were used to determine interfractional translations, rotations, and dilations of the prostate. We used hybrid imaging: The markers were automatically detected in two pretreatment planar X-ray projections; their actual position in three-dimensional space was reconstructed from these images at first. The structure set comprising prostate, seminal vesicles, and adjacent rectum wall was transformed accordingly in 6 degrees of freedom. Shapes of IMRT segments were geometrically adapted in a class solution forward-planning approach, derived within seconds on-site and treated immediately. Intrafractional movements were followed in MV electronic portal images captured on the fly. RESULTS: In 31 of 39 patients, for 833 of 1013 fractions (supine, flat couch, knee support, comfortably full bladder, empty rectum, no intraprostatic marker migrations >2 mm of more than one marker), the online aperture adaptation allowed safe reduction of margins clinical target volume-planning target volume (prostate) down to 5 mm when only interfractional corrections were applied: Dominant L-R rotations were found to be 5.3° (mean of means), standard deviation of means ±4.9°, maximum at 30.7°. Three-dimensional vector translations relative to skin markings were 9.3 ± 4.4 mm (maximum, 23.6 mm). Intrafractional movements in 7.7 ± 1.5 min (maximum, 15.1 min) between kV imaging and last beam's electronic portal images showed further L-R rotations of 2.5° ± 2.3° (maximum, 26.9°), and three-dimensional vector translations of 3.0 ±3.7 mm (maximum, 10.2 mm). Addressing intrafractional errors could further reduce margins to 3 mm. CONCLUSION: We demonstrated the clinical feasibility of an online adaptive image-guided, intensity-modulated prostate protocol on a standard linear accelerator to correct 6 degrees of freedom of internal organ motion, allowing safe and straightforward implementation of margin reduction and dose escalation.

Prostate cancer radiotherapy in Austria: overview on number of patients, intention to treat, and treatment techniques based on data from 2007.

PURPOSE: Aim of this analysis was to assess the current status of prostate cancer radiotherapy in Austria and compare these numbers to patients treated with surgery. MATERIAL AND METHODS: A questionnaire was sent to all 14 Austrian departments asking about numbers of prostate cancer patients treated and indication of treatment (primary, postoperative), as well as the treatment technique used (3D-CRT, IMRT, brachytherapy), treatment volumes (with/without pelvic irradiation), dose applied, and differences in treatment concepts. Data investigated were based on the year 2007. RESULTS: Of the 14 departments (65%), 9 departments decided to participate. A total of 1,191 prostate cancer patients were treated (847 primary, 344 postoperative). Primary patients were treated by external beam technique (91%) and permanent interstitial brachytherapy (9%). All postoperative patients were treated by 3D-CRT. Dose ranged from 70-78 Gy for primary patients and from 60-72 Gy for postoperative patients. A risk-adapted dose prescription was performed in 5 centers. Additional pelvic lymph node irradiation was based on signs of positive nodes in 4 departments and based on Roach formula/Partin table in 5 departments. CONCLUSION: About 25% of prostate cancer patients receive primary radiotherapy. This number reflects a high potential to conduct national studies. Treatment technique and dose applied was in all centers investigated in accordance with the German S3 guidelines.

A strategy for the use of image-guided radiotherapy (IGRT) on linear accelerators and its impact on treatment margins for prostate cancer patients.

BACKGROUND AND PURPOSE: In external beam radiotherapy of prostate cancer, the consideration of various systematic error types leads to wide treatment margins compromising normal tissue tolerance. We investigated if systematic set-up errors can be reduced by a set of initial image-guided radiotherapy (IGRT) sessions. PATIENTS AND METHODS: 27 patients received daily IGRT resulting in a set of 882 cone-beam computed tomographies (CBCTs). After matching to bony structures, we analyzed the dimensions of remaining systematic errors from zero up to six initial IGRT sessions and aimed at a restriction of daily IGRT for 10% of all patients. For threshold definition, we determined the standard deviations (SD) of the shift corrections and selected patients out of this range for daily image guidance. To calculate total treatment margins, we demanded for a cumulative clinical target volume (CTV) coverage of at least 95% of the specified dose in 90% of all patients. RESULTS: The gain of accuracy was largest during the first three IGRTs. In order to match precision and workload criteria, thresholds for the SD of the corrections of 3.5 mm, 2.0 mm and 4.5 mm in the left-right (L-R), cranial-caudal (C-C), and anterior-posterior (A-P) direction, respectively, were identified. Including all other error types, the total margins added to the CTV amounted to 8.6 mm in L-R, 10.4 mm in C-C, and 14.4 mm in A-P direction. CONCLUSION: Only initially performed IGRT might be helpful for eliminating gross systematic errors especially after virtual simulation. However, even with daily IGRT performance, a substantial PTV margin reduction is only achievable by matching internal markers instead of bony anatomical structures.

"Augmented reality" in conventional simulation by projection of 3-D structures into 2-D images: a comparison with virtual methods.

BACKGROUND AND PURPOSE: In this study, a new method is introduced, which allows the overlay of three-dimensional structures, that have been delineated on transverse slices, onto the fluoroscopy from conventional simulators in real time. PATIENTS AND METHODS: Setup deviations between volumetric imaging and simulation were visualized, measured and corrected for 701 patient isocenters. RESULTS: Comparing the accuracy to mere virtual simulation lacking additional X-ray imaging, a clear benefit of the new method could be shown. On average, virtual prostate simulations had to be corrected by 0.48 cm (standard deviation [SD] 0.38), and those of the breast by 0.67 cm (SD 0.66). CONCLUSION: The presented method provides an easy way to determine entity-specific safety margins related to patient setup errors upon registration of bony anatomy (prostate 0.9 cm for 90% of cases, breast 1.3 cm). The important role of planar X-ray imaging was clearly demonstrated. The innovation can also be applied to adaptive image-guided radiotherapy (IGRT) protocols.

Concepts and techniques of intraoperative radiotherapy (IORT) for breast cancer.

The standard treatment for early breast cancer comprises wide local excision, sentinel lymph node biopsy or axillary lymph node dissection, adjuvant medical treatment and radiotherapy to the whole breast. Many studies suggest that local control plays a crucial role in overall survival. The local recurrence rate is estimated to be 1% per year and varies between 4 and 7% after 5 years and up to 10 to 20% in the long-term follow up. On the basis of low local recurrence rates the concept of whole breast irradiation comes up for discussion, and partial breast irradiation (PBI) is increasingly under consideration. Intraoperative radiotherapy (IORT) is referred to as the delivery of a single high dose of irradiation directly to the tumor bed (confined target) during surgery. PBI (limited field radiation therapy, accelerated partial breast irradiation APBI) is the irradiation exclusively confined to a breast volume, the tumor surrounding tissue (tumor bed) either during surgery or after surgery without whole breast irradiation. Various methods and techniques for IORT or PBI are under investigation. The advantage of a very short radiation time or the integration of the complete radiation treatment into the surgical procedure convinces at a first glance. The promising short-term results of those studies must not fail to mention that local recurrence rates could probably increase and furthermore give rise to distant metastases and a reduction in overall survival. The combination of IORT in boost modality and whole breast irradiation has the ability to reduce local recurrence rates. The EBCTCG overview approves that differences in local treatment that substantially affect local recurrence rates would avoid about one breast cancer death over the next 15 years for every four local recurrences avoided, and should reduce 15-year overall mortality.

Austrian breast cancer patterns-of-care studies PCS93 and PCS01 versus PCS85 to identify changes in national practice.

PURPOSE: To determine the patterns of evaluation and treatment in Austrian breast cancer patients treated with surgery and radiotherapy in 1993 (PCS93) and 2001 (PCS01), and to compare these with the results of PCS85. MATERIAL AND METHODS: According to the evaluation process of the Austrian PCS85, ten randomly selected patient charts from every Austrian radiotherapy center from 1993 (n=100) as well as 2001 (n=120) were reviewed. The work-up included surgical and (histo)pathologic information, systemic therapy and detailed information on radiation therapy. RESULTS: Availability of histopathologic core data improved distinctly between 1985 and 2001. In 1985, treatment planning included fluoroscopic simulation and/or computed tomography in 55% of the cases as compared to 100% in 2001. The technical equipment in Austria changed distinctly. In 2001, 84% of the breast/chest wall fields and all regional node fields (+/- electrons) were treated by photons. Radiotherapy of the supraclavicular (77% vs. 28%), internal mammary (62% vs. 7.5%) and axillary nodes (51% vs. 5%) diminished from 1985 to 2001. A tumor bed boost was given in 34% of the patients in 1985 compared to 73% in 2001. The use of wedges (21% vs. 97%) and the number of port films (26% vs. 90%) increased substantially. CONCLUSION: Comparing both recent Austrian Patterns-of-Care surveys to the results obtained in 1985, an obvious increase in the quality level of histopathologic reporting as well as radiation treatment planning and delivery was found.

A dosimetric comparison of IORT techniques in limited-stage breast cancer.

BACKGROUND AND PURPOSE: For intraoperative radiotherapy (IORT) during breast-conserving treatment four different techniques have been addressed: interstitial brachytherapy, an inflatable balloon with a central high-dose-rate source (MammoSite), a miniature orthovolt system (Intrabeam), and linac-based electron radiotherapy (IOERT). The dosimetric properties of these methods are compared. MATERIAL AND METHODS: Planning target volumes (PTVs) of the same size but of different shapes are assumed, corresponding to the technique's specific situs. Dose distributions for the PTVs and for surrounding tissues are demonstrated by dose-volume histograms and a list of physical parameters. A dose inhomogeneity index (DII) is introduced to describe the deviation of a delivered from the prescribed dose, reaching its minimal value 0 in case of perfect homogeneity. RESULTS: In terms of DII, IOERT reaches the lowest value followed by the MammoSite, the Intrabeam and interstitial implants. The surrounding tissues receive the smallest average dose with IOERT, closely followed by the orthovolt system. CONCLUSION: When comparing simplified geometric figures, IOERT delivers the most homogeneous dose distributions. However, in clinical reality PTVs often present asymmetric shapes instead of ideal geometries. Due to a strictly centric dose fall-off, any system with a round central applicator will have technical limits. During IOERT margin-directed applicator guidance is possible and interstitial brachytherapy allows for polygonal dose shaping. These techniques seem to be superior for asymmetric PTV irradiation.

The Salzburg concept of intraoperative radiotherapy for breast cancer: results and considerations.

Aim of this study is to show that ipsilateral breast tumor recurrence (IBTR) after breast conserving surgery can be reduced by proper surgery and modern radiotherapy techniques. Three hundred and seventy eight women with stage I or II breast cancer had breast conserving surgery and received 51-56.1 Gy of postoperative radiation to the whole breast in 1.7 Gy fractions, but patients received different boost strategies. Group 1 (n = 188) received electron boost radiation of 12 Gy subsequent to the irradiation to the whole breast, group 2 (n = 190) received intraoperative electron boost radiation of 9 Gy directly to the tumor bed, followed by whole breast irradiation. After a median follow up period of 81.0 months in group 1 and a median follow up period of 51.1 months in group 2, 12 IBTRs (6.4%) could be observed in group 1 and no IBTR could be observed in group 2 (0.0%). The 5-year actuarial rates of IBTR were 4.3% (95% CI, 1.9-8.3%) and 0.0% (95% CI, 0.0-1.9%), respectively (p = 0.0018). The 5-year actuarial rates of distant recurrence were 8.6% (95% CI, 4.9-13.5%) and 4.2% (95% CI, 1.8-8.2%), respectively (p = 0.08). The 5 year disease-free survival rates were 90.9% (95% CI, 85.8-94.7%) in group 1 and 95.8% (95% CI, 91.8-98.2%) in group 2 (p = 0.064). Immediate IORT-boost and whole breast irradiation yields excellent local control at 5 years, and was associated with a statistically significant decreased rate of IBTR compared with a similar cohort of patients treated with whole breast irradiation and conventional electron boost.

Patterns of care in radiotherapy of breast cancer in Austria 1985: data acquisition and comparison with data of US-PCS 1983.

PURPOSE: In Austria, a Patterns of Care Study (PCS) has been conducted to evaluate the standards of practice for breast cancer patients. The year 1985 was selected in order to establish a base data set. MATERIALS AND METHODS: At all nine radiation therapy facilities active in patient treatment in 1985, ten patients charts were randomly selected and reviewed. Evaluation of the radiotherapeutic standards was the principal purpose, however, surgical and histopathological parameters were also considered. RESULTS: Results of the Austrian PCS (including 90 patients) were compared with the "1983 Patterns of Care Process Survey for Definitive Breast Irradiation" performed in 1983 in the U.S. (including 191 patients). Documentation of pathologic tumour size (83% vs. 73%), histologic tumour subtype (99% vs. 97%) and microscopic margin analysis (60% vs. 51%) showed comparable results. Technical equipment was obviously quite different in the two countries, cobalt therapy was used in 25% in the US-PCS compared to 71% in the Austrian PCS. A clear difference also was obtained concerning the use of wedges for tangential breast/thoracic wall fields (64% vs. 21%) and the frequency of portal films (93% vs. 26%). CONCLUSIONS: Comparing both PCS studies, we found overall many similarities. Differences could be obtained in the quality level of radiation treatment, as for example use of wedges for tangential fields and the number of portal films. In a next step, a further Austrian PCS is planned to compare the Austrian base data from 1985 with quality standards from 1993 and 2001.