Planning Target Volume Definition Research Articles

On PTV definition for glioblastoma based on fiber tracking of diffusion tensor imaging data.

Radiotherapy (RT) is commonly applied for the treatment of glioblastoma multiforme (GBM). Following the planning target volume (PTV) definition procedure standardized in guidelines, a 20% risk of missing non-local recurrences is present. Purpose of this study was to evaluate whether diffusion tensor imaging (DTI)-based fiber tracking may be beneficial for PTV definition taking into account the prediction of distant recurrences. 56 GBM patients were examined with magnetic resonance imaging (MRI) including DTI performed before RT after resection of the primary tumor. Follow-up MRIs were acquired in three month intervals. For the seven patients with a distant recurrence, fiber tracking was performed with three algorithms and it was evaluated whether connections existed from the primary tumor region to the distant recurrence. It depended strongly on the used tracking algorithm and the used tracking parameters whether a connection was observed. Most of the connections were weak and thus not usable for PTV definition. Only in one of the seven patients with a recurring tumor, a clear connection was present. It seems unlikely that DTI-based fiber tracking can be beneficial for predicting distant recurrences in the planning of PTVs for glioblastoma multiforme.

Variability in lymph node irradiation in patients with breast cancer-results from amulti-center survey in German-speaking countries.

Lymph node irradiation in breast cancer has gained complexity due to recently published studies and technical innovations which then led to changes in international guidelines. We sought to determine real-time variability in lymph node irradiation in clinical practice in German-speaking countries. The Department of Radiation Oncology, Technical University of Munich (TUM), developed an online-based questionnaire focusing on the indication, target definition, and treatment technique of lymph node irradiation in patients with breast cancer. The invitation to participate in the survey was sent to members of the German Society of Radiation Oncology (DEGRO) by e‑mail. The results of the survey were exported from the online platform into SPSS for adetailed analysis. In total, 100physicians completed the questionnaire between 05/2019 and 06/2019. Despite the existence of several treatment and contouring guidelines, we observed large variability of lymph node irradiation: The guideline recommendation for internal mammary irradiation is not consistently implemented in clinical practice and irradiation of the axilla after positive SLNB (sentinel lymph node biopsy) or ALND (axillary lymph node dissection) is handled very differently. Furthermore, in most clinics, the ESTRO (European Society for Therapeutic Radiology and Oncology) contouring consensus is not used, and PTV (planning target volume) definitions and margins vary considerably. Further clinical studies should be performed with aparticular focus on radiotherapy for lymphatic drainage to support and amend the existing guidelines. These studies should establish amore standardized treatment of the lymph node regions in clinical practice. Quality assurance should enforce broad implementation of consensus recommendations.

Definition of fields margins for the optimized 2D radiotherapy of prostate carcinoma.

Prostate cancer (PCa) is one of the most common malignancies in men both in western and developing countries. Radiotherapy (RT) is an important therapeutic option. New technologies (including 3D, intensity modulated RT, image-guided RT and, volumetric modulated arc therapy) have been introduced in the last few decades with progressive improvement of clinical outcomes. However, in many developing countries, the only treatment option is the traditional two-dimensional (2D) technique based on standard simulation. The guidelines for 2D field definition are still based on expert's opinions. The aim of the present study was to propose new practical guidelines for 2D fields definition based on 3D simulation in PCa. A total of 20 patients were enrolled. Computed tomography-simulation and pelvic magnetic resonance images were merged to define the prostate volumes. Clinical Target Volume (CTV) was defined using the European Organisation for Research and Treatment of Cancer guidelines in consideration of the four risk categories: Low, intermediate, and high risk with or without seminal vesicles involvement, respectively. Planning Target Volume (PTV) was defined by adding 10 mm to the CTV. For each category, two treatment plans were calculated using a cobalt source or 10 MV photons. Progressive optimization was achieved by evaluating 3D dose distribution. Finally, the optimal distances between field margins and radiological landmarks (bones and rectum with contrast medium) were defined. The results were reported in tabular form. Both field margins (PTV D98% >95%) needed to adequately irradiate all patients and to achieve a similar result in 95% of the enrolled patients are reported. Using a group of patients with PCa and based on a 3D planning analysis, we propose new practical guidelines for PCa 2D-RT based on current criteria for risk category and CTV, and PTV definition.

Setup errors in radiation therapy for thoracic tumor patients of different body mass index.

PurposeTo assess the setup errors in radiation therapy for thoracic tumors patients of different somatotypes, and to seek an individualized mathematical basis for defining the planning target volume (PTV).MethodsSixty patients with thoracic tumors were divided into four somatotypes according to their body mass index (BMI), and their body positions were setup by two groups of technicians independently. CT simulations were performed and the reconstructed radiography was digitally generated as reference images for location verification and error measurement. By setting positioning error ranges, the within‐range positioning correction rate was compared among groups.ResultsPosition setups for patients in the emaciated group, moderate group, and overweight group were relatively stable (with minor setup error differences between the two groups of technicians). In emaciated group, moderate group, overweight group, and obese group, setup errors in the right–left direction (R‐L) were 2.2 ± 1.3 mm, 2.2 ± 1.6 mm, 3.9 ± 3.1 mm, and 8.8 ± 3.5 mm, respectively; whereas the setup errors in the four groups in the superior–inferior(S‐I) direction were 2.4 ± 1.8 mm, 2.1 ± 1.9 mm, 3.2 ± 2.6 mm, and 5.4 ± 3.5 mm, and in the anterior–posterior (A‐P) direction were 2.2 ± 1.7 mm, 1.9 ± 1.9 mm, 3.2 ± 2.9 mm, and 6.2 ± 4.2 mm, respectively. Moreover, in the moderate group, the positioning correction rate in the three directions (R‐L, S‐I, and A‐P) was 20%, 9%, 8% within the error range of 5–10 mm, and 3%, 0%, 1% with a more than 10 mm error range. However, in overweight group and obese group, the positioning correction rate in these three directions (also with a more than 10 mm error range) was 23%, 27%, 19% and 21%, 16%, 23%, respectively.ConclusionsIn radiation therapy for patients with thoracic tumors, the definition of PTV should be individualized. Meanwhile, with the increase in BMI, positioning correction rate has a tendency to rise too.

Radiation and concomitant chemotherapy for patients with glioblastoma multiforme.

Postoperative external beam radiotherapy was considered the standard adjuvant treatment for patients with glioblastoma multiforme until the advent of using the drug temozolomide (TMZ) in addition to radiotherapy. High-dose volume should be focal, minimizing whole brain irradiation. Modern imaging, using several magnetic resonance sequences, has improved the planning target volume definition. The total dose delivered should be in the range of 60 Gy in fraction sizes of 1.8-2.0 Gy. Currently, TMZ concomitant and adjuvant to radiotherapy has become the standard of care for glioblastoma multiforme patients. Radiotherapy dose-intensification and radiosensitizer approaches have not improved the outcome. In spite of the lack of high quality evidence, stereotactic radiotherapy can be considered for a selected group of patients. For elderly patients, data suggest that the same survival benefit can be achieved with similar morbidity using a shorter course of radiotherapy (hypofractionation). Elderly patients with tumors that exhibit methylation of the O-6-methylguanine-DNA methyltransferase promoter can benefit from TMZ alone.

Marges dans le cancer pulmonaire : volume cible interne/volume cible anatomoclinique

The aim of this study was to carry out a review of margins that should be used for the delineation of target volumes in lung cancer, with a focus on margins from gross tumour volume (GTV) to clinical target volume (CTV) and internal target volume (ITV) delineation. Our review was based on a PubMed literature search with, as a cornerstone, the 2010 European Organisation for Research and Treatment of Cancer (EORTC) recommandations by De Ruysscher et al. The keywords used for the search were: radiotherapy, lung cancer, clinical target volume, internal target volume. The relevant information was categorized under the following headings: gross tumour volume definition (GTV), CTV–GTV margin (first tumoural CTV then nodal CTV definition), in field versus elective nodal irradiation, metabolic imaging role through the input of the PET scanner for tumour target volume and limitations of PET-CT imaging for nodal target volume definition, postoperative radiotherapy target volume definition, delineation of target volumes after induction chemotherapy; then the internal target volume is specified as well as tumoural mobility for lung cancer and respiratory gating techniques. Finally, a chapter is dedicated to planning target volume definition and another to small cell lung cancer. For each heading, the most relevant and recent clinical trials and publications are mentioned.

A Comparison of Planning Target Volume Definition by the Patient-Specific Margins and the Generic Margins for Thoracic Esophageal Cancer

To compare the centroid position and volumetric differences of planning target volume (PTV) definition by 3DCT and 4DCT, the addition of the patient-specific margins, or the generic margins for the thoracic primary esophageal cancer.

Optimized Planning Target Volume for Intact Cervical Cancer

To model interfraction clinical target volume (CTV) variation in patients with intact cervical cancer and design a planning target volume (PTV) that minimizes normal tissue dose while maximizing CTV coverage. We analyzed 50 patients undergoing external-beam radiotherapy for intact cervical cancer using daily online cone-beam computed tomography (CBCT). The CBCTs (n = 972) for each patient were rigidly registered to the planning CT. The CTV was delineated on the planning CT (CTV(0)) and the set of CBCTs ({CTV(1)-CTV(25)}). Manual (n = 98) and automated (n = 668) landmarks were placed over the surface of CTV(0) with reference to defined anatomic structures. Normal vectors were extended from each landmark, and the minimum length required for a given probability of encompassing CTV(1)-CTV(25) was computed. The resulting expansions were used to generate an optimized PTV. The mean (SD; range) normal vector length to ensure 95% coverage was 4.3 mm (2.7 mm; 1-16 mm). The uniform expansion required to ensure 95% probability of CTV coverage was 13 mm. An anisotropic margin of 20 mm anteriorly and posteriorly and 10 mm superiorly, inferiorly, and laterally also would have ensured a 95% probability of CTV coverage. The volume of the 95% optimized PTV (1470 cm(3)) was significantly lower than both the anisotropic PTV (2220 cm(3)) and the uniformly expanded PTV (2110 cm(3)) (p < 0.001). For a 95% probability of CTV coverage, normal lengths of 1-3 mm were found along the superior and lateral regions of CTV(0), 5-10 mm along the interfaces of CTV(0) with the bladder and rectum, and 10-14 mm along the anterior surface of CTV(0) at the level of the uterus. Optimizing PTV definition according to surface landmarking resulted in a high probability of CTV coverage with reduced PTV volumes. Our results provide data justifying planning margins to use in practice and clinical trials.

4D-CT-based target volume definition in stereotactic radiotherapy of lung tumours: Comparison with a conventional technique using individual margins

Purpose To investigate the dosimetric benefit of integration of 4D-CT in the planning target volume (PTV) definition process compared to conventional PTV definition using individual margins in stereotactic body radiotherapy (SBRT) of lung tumours. Material and methods Two different PTVs were defined: PTV conv consisting of the helical-CT-based clinical target volume (CTV) enlarged isotropically for each spatial direction by the individually measured amount of motion in the 4D-CT, and PTV 4D encompassing the CTVs defined in the 4D-CT phases displaying the extremes of the tumour position. Tumour motion as well as volumetric and dosimetric differences and relations of both PTVs were evaluated. Results Volumetric examinations revealed a significant reduction of the mean PTV by 4D-CT from 57.7 to 40.7 cm 3 (31%) ( p < 0.001). A significant inverse correlation was found for the motion vector and the amount of inclusion of PTV 4D in PTV conv ( r = −0.69, 90% confidence limits: −0.87 and −0.34, p = 0.007). Mean lung dose (MLD) was decreased significantly by 17% ( p < 0.001). Conclusions In SBRT of lung tumours the mere use of individual margins for target volume definition cannot compensate for the additional effects that the implementation of 4D-CT phases can offer.

Surface Dose in the Treatment of Breast Cancer with Helical Tomotherapy

Investigation of the effects of breathing motion- and misregistration-induced errors on the superficial dose in the treatment of breast cancer using helical tomotherapy (HT). Surface dose measurements were performed with thermoluminescence dosimetry (TLD). Two treatment plans with different planning target volume (PTV) definitions of the left breast were used: PTVskin had its ventral border exactly on skin level, while PTVair included also a 10-mm extension ventral to the PTVskin. With a thoracic static phantom, misregistration errors in an HT were simulated. A dynamic phantom was used to simulate a breathing patient during HT. Surface doses of breast cancer patients were measured both for an HT (179 points) and a conventional three-dimensional conformal treatment (70 points). In the static phantom misregistration setup, dose deviations of -31.9% for PTVskin to +35.4% for PTVair could be observed. The dynamic phantom measurements resulted in surface dose deviations from those in a static position between 0.8% and 3.8% without a significant difference for the PTV definitions. The measured surface doses on patients averaged (mean +/- standard deviation) 1.65 +/- 0.13 Gy for the HT and 1.42 +/- 0.11 Gy for the three-dimensional conformal treatment. HT enables a homogeneous and reproducible surface dose with small dose deviations in the treatment of breast cancer. HT is a feasible method to treat breast cancer under free shallow breathing of the patient using a treatment plan with a ventral PTV border on the skin level.

Generic Planning Target Margin for Rectal Cancer Treatment Setup Variation

To calculate the generic planning target margin (GPTM) for patients receiving radiation therapy (RT) for rectal cancer placed in a prone position with a customized cradle for small-bowel exclusion. A total of 25 consecutive rectal cancer patients were treated for 25 or 28 fractions in a prone position using a cradle to maximize small bowel exclusion. Treatment planning computed tomography (CT) scans were used to create orthogonally digitally reconstructed radiographs (DRRs) for portal image registration, which were compared with daily portal images from an electronic portal-imaging device (EPID). Translation values needed to align the DRRs and EPIDs were recorded for the superior to inferior (SI), right to left (RL), and anterior to posterior (AP) directions, and used to calculate the GPTM using the four-parameter model. Age, weight, and body mass index were tested compared with the setup variation using a Pearson correlation and a t test for significance. Gender versus setup variation was compared with a t test. A total of 1,723 EPID images were reviewed. The GPTM was 10 mm superior, 8 mm inferior, 7 mm RL and 10 mm AP. Age and gender were unrelated to setup variation. Weight was significantly associated with systematic AP variation (p < 0.05). BMI was significantly associated with systematic SI (p < 0.05) and AP (p < 0.01) variation and random RL variation (p < 0.05). The GPTM for rectal cancer is asymmetric with a maximum of 10 mm in the superior, anterior and posterior dimensions. Body mass index may effect setup variation. Research using advanced treatment planning should include these margins in the planning target volume definition.

Computed tomography for excision cavity localization and 3D-treatment planning in partial breast irradiation with high-dose-rate interstitial brachytherapy

Background and purpose When high-dose-rate brachytherapy is used for partial breast irradiation (PBI) precise pre-implant definition of planning target volume (PTV) and implant geometry is required. After implantation, accurate PTV localization, catheter reconstruction and optimization of dose distribution are needed for good PTV coverage and dose conformity. We applied image-guidance using computed tomography (CT) for pre-implant PTV definition and post-implant dosimetry. Materials and methods In 54 patients implant geometry was designed by external beam virtual simulation. A template was placed over dummy beam digitally reconstructed radiographs displaying PTV. Needle entrance and exit points were defined and marked on the patient’s skin to serve as landmarks during implantation. After implantation, in 46/54 patients PTV was defined, catheters were reconstructed and active lengths in the catheters were specified using CT-based-3D planning system. Dosimetry was performed with a Plato-Nucletron treatment planning system. Results Post-implantation CT visualized precise catheter placement with respect to the PTV in all patients. CT-based treatment planning provided good coverage of PTV and homogeneous dose distribution. Conclusions In post-operative PBI with high-dose-rate brachytherapy CT-based pre-implant definition of implant geometry ensures adequate PTV coverage. After implantation, CT-based 3D-treatment planning software ensures exact PTV localization and catheter reconstruction, and dose distribution optimization.

Craniospinal irradiation using a forward planned segmented field technique

Craniospinal irradiation is technically demanding due to the complex shape of the planning target volume (PTV). Radiotherapy treatment techniques have evolved over time as imaging and radiotherapy treatment technology have improved. However, most are variations on a class solution utilizing a prone patient position with two shaped lateral cranial portals and a matched posterior spinal portal with moving junctions. Major areas of difficulty remain with the accurate definition of the PTV and achieving a homogeneous dose within it, especially at the junctions. We describe a three-dimensionally (3D) planned craniospinal radiation technique that permits rapid image acquisition with reduced localization time, simplified spinal PTV definition and standardized cranial PTV definition. Improved dose homogeneity within the PTV is achieved by use of a segmented "field-in-field" technique (forward planned intensity-modulated radiotherapy (IMRT)) in place of customized compensators. This has negated the requirement for constructing physical compensators. Autosequencing for field delivery enables the junction to be "moved" during a single fraction and reduces the overall treatment time, an important consideration when treating very young patients.

Automated functional image-guided radiation treatment planning for rectal cancer

Computer tomography-based (CT-based) tumor-volume definition is time consuming and is subject to clinical interpretation. CT is not accessible for standardized algorithms for the purpose of treatment-volume planning. We have evaluated the accuracy of target-volume definition based on the positron emission tomography (PET) data from an integrated PET/CT system with 2-[(18)F]fluoro-2-deoxy-D-glucose (FDG) for standardized target-volume delineation. Eleven patients with rectal cancer who were undergoing preoperative radiation therapy (RT) were studied. A standardized region-growing algorithm was tested to replace the CT-derived gross tumor volume by the PET-derived gross tumor volume (PET-GTV) or the biologic target volume (BTV). A software tool was developed to automatically delineate the appropriate tumor volume as defined by the FDG signal, the PET-GTV, and the planning target volume (PTV). The PET-derived volumes were compared with the target volumes from CT. The BTV defined for appropriate GTV assessment was set at a single peak threshold of 40% of the signal of interest. Immediate treatment volume definition based on the choice of a single-tumor volume-derived PET-voxel resulted in a tumor volume that strongly correlated with the CT-derived GTV (r(2) = 0.84; p < 0.01) and the volume as assessed on subsequent anatomic-pathologic analysis (r(2) = 0.77; p < 0.01). In providing sufficient extension margins from the CT-derived GTV and the PET-derived GTV, to PTV, respectively, the correlation of the CT-derived and PET-derived PTV was sufficiently accurate for PTV definition for external-beam therapy (r(2) = 0.96; p < 0.01). Automated segmentation of the PET signal from rectal cancer may allow immediate and sufficiently accurate definition of a preliminary working PTV for preoperative RT. If required, correction for anatomic precision and geometric resolution may be applied in a second step. Computed PET-based target-volume definition could be useful for the definition of standardized simultaneous internal-boost volumes for intensity-modulated radiation therapy (IMRT) based on biologic target volumes.

Motion‐encoded dose calculation through fluence/sinogram modification

Conventional radiotherapy treatment planning systems rely on a static computed tomography (CT) image for planning and evaluation. Intra/inter-fraction patient motions may result in significant differences between the planned and the delivered dose. In this paper, we develop a method to incorporate the knowledge of intra/inter-fraction patient motion directly into the dose calculation. By decomposing the motion into a parallel (to beam direction) component and perpendicular (to beam direction) component, we show that the motion effects can be accounted for by simply modifying the fluence distribution (sinogram). After such modification, dose calculation is the same as those based on a static planning image. This method is superior to the "dose-convolution" method because it is not based on "shift invariant" assumption. Therefore, it deals with material heterogeneity and surface curvature very well. We test our method using extensive simulations, which include four phantoms, four motion patterns, and three plan beams. We compare our method with the "dose-convolution" and the "stochastic simulation" methods (gold standard). As for the homogeneous flat surface phantom, our method has similar accuracy as the "dose-convolution" method. As for all other phantoms, our method outperforms the "dose-convolution." The maximum motion encoded dose calculation error using our method is within 4% of the gold standard. It is shown that a treatment planning system that is based on "motion-encoded dose calculation" can incorporate random and systematic motion errors in a very simple fashion. Under this approximation, in principle, a planning target volume definition is not required, since it already accounts for the intra/inter-fraction motion variations and it automatically optimizes the cumulative dose rather than the single fraction dose.

Set-up improvement in head and neck radiotherapy using a 3D off-line EPID-based correction protocol and a customised head and neck support

Purpose: First, to investigate the set-up improvement resulting from the introduction of a customised head and neck (HN) support system in combination with a technologist-driven off-line correction protocol in HN radiotherapy. Second, to define margins for planning target volume definition, accounting for systematic and random set-up uncertainties. Methods and materials: In 63 patients 498 treatment fractions were evaluated to develop and implement a 3D shrinking action level correction protocol. In the comparative study two different HN-supports were compared: a flexible ‘standard HN-support’ and a ‘customised HN-support”. For all three directions ( x, y and z) random and systematic set-up deviations (1 S.D.) were measured. Results: The customised HN-support improves the patient positioning compared to the standard HN-support. The 1D systematic errors in the x, y and z directions were reduced from 2.2–2.3 mm to 1.2–2.0 mm (1 S.D.). The 1D random errors for the y and z directions were reduced from 1.6 and 1.6 mm to 1.1 and 1.0 mm (1 S.D.). The correction protocol reduced the 1D systematic errors further to 0.8–1.1 mm (1 S.D.) and all deviations in any direction were within 5 mm. Treatment time per measured fraction was increased from 10 to 13 min. The total time required per patient, for the complete correction procedure, was approximately 40 min. Conclusions: Portal imaging is a powerful tool in the evaluation of the department specific patient positioning procedures. The introduction of a comfortable customised HN-support, in combination with an electronic portal imaging device-based correction protocol, executed by technologists, led to an improvement of overall patient set-up. As a result, application of proposed recipes for CTV–PTV margins indicates that these can be reduced to 3–4 mm.

Computed tomogram prior to prostatectomy. Advantage in defining planning target volumes for postoperative adjuvant radiotherapy in patients with stage C prostate cancer?

To evaluate the influence of a preoperative computed tomogram (CT) on delineation of the planning target volume (PTV) for adjuvant radiation therapy of pT3 pN0 prostate cancer. PTVs of ten patients who had an additional preoperative CT examination were contoured by three independent radiation oncologists. PTV included the former prostatic bed and seminal vesicles with a safety margin. First PTVs were drawn without knowledge of the preoperative CTs and in a second attempt, this procedure was repeated with these CTs available for visual comparison. Changes in PTV dimensions for every patient were analyzed. In 93% of all PTVs there was a decision to increase the PTV after viewing the preoperative CT images. Mean PTV length increased from 7.3 to 8.4 cm and PTV volumes expanded 26% from 244 to 308 cm3. These differences were statistically significant for all three participating radiation oncologists. Planning target volume definition probably is a critical factor in adjuvant radiation therapy after radical prostatectomy. As there is a considerable incertainty in PTV definition a preoperative CT is helpful and therefore may have beneficial influence on results.

Planning target volume definition in dose-escalation studies.

Planning target volume definition in dose-escalation studies.

The role of iliopelvic lymphoscintigraphy in the definition of target volumes for radiation therapy of pelvic tumors

The role of iliopelvic lymphoscintigraphy in the definition of target volumes for radiation therapy of pelvic tumors

Brachytherapy

I read with great interest the article by Koot et al.1 comparing the results of two completely different concepts of interstitial brachytherapy in the treatment of patients with glioblastoma multiforme (GBM). The regimens differ with regard to the extent of initial surgery (biopsy vs. cytoreductive surgery), the isotope used (iodine-125 vs. iridium-192), the dose given via external beam radiotherapy (EBRT) (10–30 grays [Gy] vs. 60 Gy), the brachytherapy target volume (contrast-enhancing region without margin vs. that with a 5-mm margin), and the timing of the treatment (initial brachytherapy with simultaneous EBRT vs. initial EBRT followed by interstitial boost). Despite these contrasting concepts, a median survival of 17 months and 16 months, respectively, was observed in defined subgroups (those age > 30 years with a Karnofsky performance score ≥ 70 and a nonmidline tumor) from both cohorts compared with a median survival of 10 months in a control group. Unfortunately, the authors missed an opportunity to shed more light on a central, unresolved issue concerning radiation therapy for GBM: the criteria defining the volume to be treated with higher-than-conventional doses. First, the report by Koot et al. lacks information concerning how the brachytherapy planning target volume (PTV) was defined. Apparently, the PTV definition was based on contrast enhancement on computed tomography (CT), and in some cases magnetic resonance imaging (MRI) was used instead or as additional information. Taking into account that these two imaging modalities already differ substantially in outlining malignant gliomas,2 it is essential to know how CT and MRI contributed to the PTV definition (combined volume or an overlap of both methods?). In addition, there was no information at all presented with regard to the definition of EBRT volumes and the imaging and criteria used to define disease progression. The authors only state that in the 1 cohort, 51% of the patients recurred “outside the margins of the isodose distribution” (the prescription isodose?) and that in the other group, all recurrences occured “at the original site” (inside the brachytherapy PTV or inside the EBRT PTV?). Interstitial brachytherapy in the treatment of GBM competes with noninvasive modalities such as high-dose proton/photon radiotherapy3 and stereotactic EBRT boost after conventional radiotherapy, with the latter currently being studied in what to my knowledge are ongoing randomized trials.4, 5 Both concepts have demonstrated comparable, although mixed, results in Phase II studies, with estimated survival advantages of 5–11 months compared with conventional treatment.4, 6 In contrast to the report by Koot et al.,1 these studies presented a thorough analysis of patterns of recurrence, demonstrating a true shift from the common central recurrence after conventional radiotherapy7 to marginal recurrence after central high-dose treatment. For example, Fitzek et al. observed histologically confirmed recurrent tumor within the high-dose volume in only 1 case despite a high reoperation rate of 57% in a group of 23 GBM patients treated with 90 cobalt gray equivalent with proton/photon irradiation.3 In contrast, new MRI enhancement after treatment within that same volume was found in 78% of patients, underscoring the difficulty in differentiating between necrosis and tumor recurrence. In a series of 78 GBM patients treated with a stereotactic EBRT boost, Shrieve et al. found only 38% of recurrences developed within 2 cm of the boost prescription isodose.6 To interpret the results of the study by Koot et al.,1 it would be helpful to know exactly where the recurrences (defined by imaging or pathology at reoperation) occured with regard to PTV or treated volume. If there is any benefit to high-dose radiotherapy by any method in the treatment of GBM, it lies in the treatment's ability to sterilize the central region of the solid tumor. Although this potential benefit must be weighed carefully against the risk of radiation-induced necrosis, several investigators have called for an extension of the high-dose target volume beyond the area of contrast enhancement.3, 8 The definition of such extended volumes may include additional information regarding tumor outline using modalities such as single photon computed emission tomography9 or transcranial sonography.10 In any case, the treatment of GBM patients beyond conventional radiotherapy doses and a potential optimization of current concepts calls for a clear definition of the target volumes used and a particularly thorough documentation of the patterns of tumor recurrence. [The authors were invited to reply and declined the invitation.] Dirk Vordermark M.D.*, * Department of Radiation Oncology, University of Wuerzburg, Wuerzburg, Germany