David Pasquier

Atypical and Malignant Meningioma: Outcome and Prognostic Factors in 119 Irradiated Patients. A Multicenter, Retrospective Study of the Rare Cancer Network

PURPOSE To retrospectively analyze and assess the outcomes and prognostic factors in a large number of patients with atypical and malignant meningiomas. METHODS AND MATERIALS Ten academic medical centers participating in this Rare Cancer Network contributed 119 cases of patients with atypical or malignant meningiomas treated with external beam radiotherapy (EBRT) after surgery or for recurrence. Eligibility criteria were histologically proven atypical or anaplastic (malignant) meningioma (World Health Organization Grade 2 and 3) treated with fractionated EBRT after initial resection or for recurrence, and age >18 years. Sex ratio (male/female) was 1.3, and mean (+/-SD) age was 57.6 +/- 12 years. Surgery was macroscopically complete (Simpson Grades 1-3) in 71% of patients; histology was atypical and malignant in 69% and 31%, respectively. Mean dose of EBRT was 54.6 +/- 5.1 Gy (range, 40-66 Gy). Median follow-up was 4.1 years. RESULTS The 5- and 10-year actuarial overall survival rates were 65% and 51%, respectively, and were significantly influenced by age >60 years (p = 0.005), Karnofsky performance status (KPS) (p = 0.01), and high mitotic rate (p = 0.047) on univariate analysis. On multivariate analysis age >60 years (p = 0.001) and high mitotic rate (p = 0.02) remained significant adverse prognostic factors. The 5- and 10-year disease-free survival rates were 58% and 48%, respectively, and were significantly influenced by KPS (p = 0.04) and high mitotic rate (p = 0.003) on univariate analysis. On multivariate analysis only high mitotic rate (p = 0.003) remained a significant prognostic factor. CONCLUSIONS In this multicenter retrospective study, age, KPS, and mitotic rate influenced outcome. Multicenter prospective studies are necessary to clarify the management and prognostic factors of such a rare disease.

Adjuvant and Salvage Radiotherapy After Prostatectomy for Prostate Cancer: A Literature Review

PURPOSE Given that postprostatectomy recurrence of prostate cancer occurs in 10-40% of patients, the best use of immediate postoperative radiotherapy (RT) in high-risk patients and salvage RT for biochemical recurrence remains a topic of debate. We assessed the levels of evidence (in terms of efficacy, prognostic factors, and toxicity) for the following treatment strategies: immediate postoperative RT alone, salvage RT alone, and the addition of androgen deprivation therapy to the two RT strategies. METHODS AND MATERIALS A systematic literature search for controlled randomized trials, noncontrolled trials, and retrospective studies between 1990 and 2008 was performed on PubMed, CancerLit, and MEDLINE. Only relevant articles that had appeared in peer-reviewed journals were selected. We report on the levels of evidence (according to the National Cancer Institute guidelines) supporting the various treatment strategies. RESULTS Immediate postoperative RT improves biochemical and clinical progression-free survival (Level of evidence, 1.ii) but has no significant effect on metastasis-free survival or overall survival. A pathologic review is of particular importance for correctly analyzing the treatment strategies. Low-grade morbidity has been significantly greater in the postoperative groups, but no severe toxicity has been observed. The influence of immediate postoperative RT on postprostatectomy continence appears to be slight; therefore, immediate postoperative RT should be considered in patients with major risk factors for local relapse (Level of evidence, 1.ii). On the basis of extensive retrospective data, salvage RT is effective in biochemical relapse after prostatectomy; some patients with few adverse prognostic factors might also benefit from salvage RT (Level of evidence, 3.ii). The addition of androgen deprivation therapy to immediate postoperative or salvage RT has only been supported by weak, retrospective data (Level of evidence, 3.ii). CONCLUSION Prospective randomized trials are needed to compare immediate postoperative RT with salvage RT and to assess the value of androgen deprivation therapy in this setting.

MRI alone simulation for conformal radiation therapy of prostate cancer: technical aspects.

The value of MRI in defining target volumes and organs at risk is established. Numerous difficulties appear to stand in the way of using MRI alone in dose planning, with the result that this imaging modality is used in most cases in conjunction with computerized X-ray tomography (CT). The aim of this paper is to appreciate these difficulties: geometrical distortion, chemical shifts, dosimetric accuracy. Geometrical distortion measurements were carried out on two 1.5 T MR scanners and the effect of chemical shift and magnetic susceptibility were evaluated in volunteers. The effect on dosimetric calculations of uncertainty in determining electron densities was evaluated too. Geometrical distortion remained at small values: less than 2 mm and 3 mm for field of view of 20 cm and 45 cm. The chemical shift and magnetic susceptibility values obtained, ranging from 0.3 to 3 mm, were well below the theoretical values. The assignment of relative electron densities to only two structures in MR images seems to permit dose planning that is identical with that obtained with CT. None of the technical obstacles mentioned represents a stumbling block. The access to MRI facility could represent a persisting problem

A Dosimetric Comparison of Tomotherapy and Volumetric Modulated Arc Therapy in the Treatment of High-Risk Prostate Cancer With Pelvic Nodal Radiation Therapy

PURPOSE To compare the dosimetric results of volumetric modulated arc therapy (VMAT) and helical tomotherapy (HT) in the treatment of high-risk prostate cancer with pelvic nodal radiation therapy. METHODS AND MATERIALS Plans were generated for 10 consecutive patients treated for high-risk prostate cancer with prophylactic whole pelvic radiation therapy (WPRT) using VMAT and HT. After WPRT, a sequential boost was delivered to the prostate. Plan quality was assessed according to the criteria of the International Commission on Radiation Units and Measurements 83 report: the near-minimal (D98%), near-maximal (D2%), and median (D50%) doses; the homogeneity index (HI); and the Dice similarity coefficient (DSC). Beam-on time, integral dose, and several organs at risk (OAR) dosimetric indexes were also compared. RESULTS For WPRT, HT was able to provide a higher D98% than VMAT (44.3 ± 0.3 Gy and 43.9 ± 0.5 Gy, respectively; P=.032) and a lower D2% than VMAT (47.3 ± 0.3 Gy and 49.1 ± 0.7 Gy, respectively; P=.005), leading to a better HI. The DSC was better for WPRT with HT (0.89 ± 0.009) than with VMAT (0.80 ± 0.02; P=.002). The dosimetric indexes for the prostate boost did not differ significantly. VMAT provided better rectum wall sparing at higher doses (V70, V75, D2%). Conversely, HT provided better bladder wall sparing (V50, V60, V70), except at lower doses (V20). The beam-on times for WPRT and prostate boost were shorter with VMAT than with HT (3.1 ± 0.1 vs 7.4 ± 0.6 min, respectively; P=.002, and 1.5 ± 0.05 vs 3.7 ± 0.3 min, respectively; P=.002). The integral dose was slightly lower for VMAT. CONCLUSION VMAT and HT provided very similar and highly conformal plans that complied well with OAR dose-volume constraints. Although some dosimetric differences were statistically significant, they remained small. HT provided a more homogeneous dose distribution, whereas VMAT enabled a shorter delivery time.

Small cell carcinoma of the urinary bladder: A retrospective, multicenter rare cancer network study of 107 patients

PURPOSE Small cell carcinomas of the bladder (SCCB) account for fewer than 1% of all urinary bladder tumors. There is no consensus regarding the optimal treatment for SCCB. METHODS AND MATERIALS Fifteen academic Rare Cancer Network medical centers contributed SCCB cases. The eligibility criteria were as follows: pure or mixed SCC; local, locoregional, and metastatic stages; and age ≥18 years. The overall survival (OS) and disease-free survival (DFS) were calculated from the date of diagnosis according to the Kaplan-Meier method. The log-rank and Wilcoxon tests were used to analyze survival as functions of clinical and therapeutic factors. RESULTS The study included 107 patients (mean [±standard deviation, SD] age, 69.6 [±10.6] years; mean follow-up time, 4.4 years) with primary bladder SCC, with 66% of these patients having pure SCC. Seventy-two percent and 12% of the patients presented with T2-4N0M0 and T2-4N1-3M0 stages, respectively, and 16% presented with synchronous metastases. The most frequent curative treatments were radical surgery and chemotherapy, sequential chemotherapy and radiation therapy, and radical surgery alone. The median (interquartile range, IQR) OS and DFS times were 12.9 months (IQR, 7-32 months) and 9 months (IQR, 5-23 months), respectively. The metastatic, T2-4N0M0, and T2-4N1-3M0 groups differed significantly (P=.001) in terms of median OS and DFS. In a multivariate analysis, impaired creatinine clearance (OS and DFS), clinical stage (OS and DFS), a Karnofsky performance status <80 (OS), and pure SCC histology (OS) were independent and significant adverse prognostic factors. In the patients with nonmetastatic disease, the type of treatment (ie radical surgery with or without adjuvant chemotherapy vs conservative treatment) did not significantly influence OS or DFS (P=.7). CONCLUSIONS The prognosis for SCCB remains poor. The finding that radical cystectomy did not influence DFS or OS in the patients with nonmetastatic disease suggests that conservative treatment is appropriate in this situation.

Ultrasound image guided patient setup for prostate cancer conformal radiotherapy

The radiotherapy planning procedure is achieved using images obtained from computed tomography (CT) or magnetic resonance imaging (MR). These images are realised before the treatment which is performed in several sessions over several weeks. At the beginning of each session, the patient has to be positioned on the treatment couch under the linear accelerator in the same position as during MR or CT imaging and planning, and the organs are assumed to be in the same place. Currently, the methods used for this repositioning are based on the external anatomy of the patient and assume that the internal structures do not move. In this study, we present a new approach, suited to clinical practice, for the automatic repositioning of patients in prostate cancer radiotherapy. It is based on localization by ultrasound images and optical stereolocalization and on a matching with images regenerated in the planning volume. The method exploits a statistical model of the prostate to automatically extract its contours. The first tests in conditions of a radiotherapy session show that the method is able to obtain a patient setup with an accuracy of about 1.4mm.

Segmentation automatique des images pour la planification dosimétrique en radiothérapie

One drawback of the growth in conformal radiotherapy and image-guided radiotherapy is the increased time needed to define the volumes of interest. This also results in inter- and intra-observer variability. However, developments in computing and image processing have enabled these tasks to be partially or totally automated. This article will provide a detailed description of the main principles of image segmentation in radiotherapy, its applications and the most recent results in a clinical context.

Surface imaging, laser positioning or volumetric imaging for breast cancer with nodal involvement treated by helical TomoTherapy

A surface imaging system, Catalyst (C‐Rad), was compared with laser‐based positioning and daily mega voltage computed tomography (MVCT) setup for breast patients with nodal involvement treated by helical TomoTherapy. Catalyst‐based positioning performed better than laser‐based positioning. The respective modalities resulted in a standard deviation (SD), 68% confidence interval (CI) of positioning of left–right, craniocaudal, anterior–posterior, roll: 2.4 mm, 2.7 mm, 2.4 mm, 0.9° for Catalyst positioning, and 6.1 mm, 3.8 mm, 4.9 mm, 1.1° for laser‐based positioning, respectively. MVCT‐based precision is a combination of the interoperator variability for MVCT fusion and the patient movement during the time it takes for MVCT and fusion. The MVCT fusion interoperator variability for breast patients was evaluated at one SD left–right, craniocaudal, ant–post, roll as: 1.4 mm, 1.8 mm, 1.3 mm, 1.0°. There was no statistically significant difference between the automatic MVCT registration result and the manual adjustment; the automatic fusion results were within the 95% CI of the mean result of 10 users, except for one specific case where the patient was positioned with large yaw. We found that users add variability to the roll correction as the automatic registration was more consistent. The patient position uncertainty confidence interval was evaluated as 1.9 mm, 2.2 mm, 1.6 mm, 0.9° after 4 min, and 2.3 mm, 2.8 mm, 2.2 mm, 1° after 10 min. The combination of this patient movement with MVCT fusion interoperator variability results in total standard deviations of patient position when treatment starts 4 or 10 min after initial positioning of, respectively: 2.3 mm, 2.8 mm, 2.0 mm, 1.3° and 2.7 mm, 3.3 mm, 2.6 mm, 1.4°. Surface based positioning arrives at the same precision when taking into account the time required for MVCT imaging and fusion. These results can be used on a patient‐per‐patient basis to decide which positioning system performs the best after the first 5 fractions and when daily MVCT can be omitted. Ideally, real‐time monitoring is required to reduce important intrafraction movement. PACS number(s): 87.53.Jw, 87.53.Kn, 87.56.Da, 87.63.L‐, 81.70.TxA surface imaging system, Catalyst (C-Rad), was compared with laser-based positioning and daily mega voltage computed tomography (MVCT) setup for breast patients with nodal involvement treated by helical TomoTherapy. Catalyst-based positioning performed better than laser-based positioning. The respective modalities resulted in a standard deviation (SD), 68% confidence interval (CI) of positioning of left-right, craniocaudal, anterior-posterior, roll: 2.4 mm, 2.7 mm, 2.4 mm, 0.9° for Catalyst positioning, and 6.1 mm, 3.8 mm, 4.9 mm, 1.1° for laser-based positioning, respectively. MVCT-based precision is a combination of the interoperator variability for MVCT fusion and the patient movement during the time it takes for MVCT and fusion. The MVCT fusion interoperator variability for breast patients was evaluated at one SD left-right, craniocaudal, ant-post, roll as: 1.4 mm, 1.8 mm, 1.3 mm, 1.0°. There was no statistically significant difference between the automatic MVCT registration result and the manual adjustment; the automatic fusion results were within the 95% CI of the mean result of 10 users, except for one specific case where the patient was positioned with large yaw. We found that users add variability to the roll correction as the automatic registration was more consistent. The patient position uncertainty confidence interval was evaluated as 1.9 mm, 2.2 mm, 1.6 mm, 0.9° after 4 min, and 2.3 mm, 2.8 mm, 2.2 mm, 1° after 10 min. The combination of this patient movement with MVCT fusion interoperator variability results in total standard deviations of patient position when treatment starts 4 or 10 min after initial positioning of, respectively: 2.3 mm, 2.8 mm, 2.0 mm, 1.3° and 2.7 mm, 3.3 mm, 2.6 mm, 1.4°. Surface based positioning arrives at the same precision when taking into account the time required for MVCT imaging and fusion. These results can be used on a patient-per-patient basis to decide which positioning system performs the best after the first 5 fractions and when daily MVCT can be omitted. Ideally, real-time monitoring is required to reduce important intrafraction movement. PACS number(s): 87.53.Jw, 87.53.Kn, 87.56.Da, 87.63.L-, 81.70.Tx.

Development of CBCT-based prostate setup correction strategies and impact of rectal distension

BackgroundCone-beam computed tomography (CBCT) image-guided radiotherapy (IGRT) systems are widely used tools to verify and correct the target position before each fraction, allowing to maximize treatment accuracy and precision. In this study, we evaluate automatic three-dimensional intensity-based rigid registration (RR) methods for prostate setup correction using CBCT scans and study the impact of rectal distension on registration quality.MethodsWe retrospectively analyzed 115 CBCT scans of 10 prostate patients. CT-to-CBCT registration was performed using (a) global RR, (b) bony RR, or (c) bony RR refined by a local prostate RR using the CT clinical target volume (CTV) expanded with 1-to-20-mm varying margins. After propagation of the manual CT contours, automatic CBCT contours were generated. For evaluation, a radiation oncologist manually delineated the CTV on the CBCT scans. The propagated and manual CBCT contours were compared using the Dice similarity and a measure based on the bidirectional local distance (BLD). We also conducted a blind visual assessment of the quality of the propagated segmentations. Moreover, we automatically quantified rectal distension between the CT and CBCT scans without using the manual CBCT contours and we investigated its correlation with the registration failures. To improve the registration quality, the air in the rectum was replaced with soft tissue using a filter. The results with and without filtering were compared.ResultsThe statistical analysis of the Dice coefficients and the BLD values resulted in highly significant differences (p<10−6) for the 5-mm and 8-mm local RRs vs the global, bony and 1-mm local RRs. The 8-mm local RR provided the best compromise between accuracy and robustness (Dice median of 0.814 and 97% of success with filtering the air in the rectum). We observed that all failures were due to high rectal distension. Moreover, the visual assessment confirmed the superiority of the 8-mm local RR over the bony RR.ConclusionThe most successful CT-to-CBCT RR method proved to be the 8-mm local RR. We have shown the correlation between its registration failures and rectal distension. Furthermore, we have provided a simple (easily applicable in routine) and automatic method to quantify rectal distension and to predict registration failure using only the manual CT contours.

A 2D/3D matching based on a hybrid approach: improvement to the imaging flow for AVM radiosurgery

A new approach of registration in multimodal imaging has been developed. Modalities involved are digital subtracted angiography (DSA, 2D) and magnetic resonance angiography (MRA, 3D). Our approach is an hybrid one, mixing feature and intensity based approaches. This approach is based on the extraction of a anatomical referential common to both MRA and DSA. The results obtained prove the methods efficiency in a clinical context. This paper present the validation methodology to make it possible the replacement of the localization DSA examination by the diagnosis one, thus avoiding supplementary costs, lost time and medical hazards for the patient and for the medical staff