Fig. 3 Image-guided radiation therapy (IGRT). Patient positioning is verified by X-ray images taken directly before treatment. Treatment images are matched to reconstructed images from the planning CT (shown in gray) by using sophisticated software to adjust the treatment table in 6 rotation axes. This guarantees a high precision in dose application. The blue figure represents a patient’s head in a stereotactic RT mask. The yellow and green beams represent the stereotactic photon beams

linear accelerator is monitored by X-rays using formerly with radiographic films and currently electronic portal imaging. Features of IGRT include daily online imaging, X-rays, cone beam CT, and megavolt CT to four-dimensional (4D) target localization. For brain tumors the combination of gantry and a planar kV imaging system leads to high-resolution diagnostic quality images of the patient in treatment position. The target tracking is by orthogonal X-ray images matched using bone or implanted markers (Fig. 3). The exposure to radiation is considerably less than using electronic portal imaging device (EPID).

IGRT has taken on greater importance with the introduction of IMRT including prolonged treatment time and the presence of steep dose gradients. The use of high fraction size in stereotactic radiation therapy requires an optimal target definition patient positioning to limit complication risk.

A cone beam CT can be made before and even during the radiation treatment in the treatment position to check the position of the patient (Jaffray et al. 2002).

3.5Recurrence and Re-irradiation

Diagnostic challenge arises in cases of recurrence in highgrade brain tumors. Often, there are post-therapeutic changes visible on MRI and CT that can develop over a long time span. In cases of contrast enhancement, it is often impossible

to differentiate between post-therapeutic changes and true tumor recurrence.

During follow-up 18F-FET PET contributes important additional information for clinical management over and above the information obtained by MRI response assessment based on RANO criteria. More accuracy is needed in cases of re-irradiation, because of the exposure of organs at risk.

4Prognosis

For the future we will pay more attention to tumor heterogeneity. We know that tumor stem cells are radioresistant while differentiated cells are more radiosensitive. It is worthwhile to learn more about these stem cells in order to optimize the treatment, for example, by modifying the fractionation scheme (Leder et al. 2014).

Conclusion

Radiation therapy plays an important role in the treatment of gliomas and prolongs the survival of the patients. The most effective and widely used technique is LINAC percutaneous radiation therapy with photons.

Radiation techniques have improved during the past decades, starting with opposed fields for whole brain irradiation leading to sophisticated intensity-modulated radiotherapy using more than 150 fields with modified fluency. By upgrading the precision of the beam, imaging modalities became increasingly important in treatment planning and in treatment application. Advanced imaging techniques will stay irreplaceable in the further progress of radiation therapy.

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2.1What Is the Surgical Target

2.2The Role of Modern Imaging in Indicating Surgery

Abstract

Current data warrant cytoreductive surgical approaches in low as well as high grade gliomas. Surgical aims vary depending on histology – speed of growth and impending malignant transformation being major aspects in low grades, while surgical improvement of preconditions for adjuvant therapy gains prognostic relevance in malignant glioma. A delicate balance between the extent of resection and functional integrity has to be kept in all of these procedures. Their planning and realization thus require reliable conceptions of tumor extension with reference to functional anatomy. Radiology and nuclear medicine provide preoperative and, to a certain extent also intraoperative insights. Additional intraoperative assistance is provided by electrophysiology and – in malignant glioma – by direct tumor visualization, which uses pharmacologic agents together with specialized optics. Emerging surgical concepts like functionally guided tissue removal or so-called supramarginal resection are still waiting for their clinical validation and for new techniques which might be able to morphologically substantiate the respective rationale.

J. Wölfer • W. Stummer (*)

Neurochirurgische Klinik, Universitätsklinikum Münster, Albert-Schweitzer-Campus 1, Geb. A1, Münster 48149, Germany e-mail: woelfer@uni-muenster.de; walter.stummer@ukmuenster.de

1Why Is Advanced Imaging Indispensable for Modern Glioma Surgery?

During the last two decades, the understanding of the value of glioma resection has undergone a change. Despite a paucity of randomized studies, a number of prospective cohort studies have provided acceptable evidence that maximal cytoreduction is a meaningful treatment option which serves to improve prognosis in patients suffering from highand low-grade gliomas alike. Nowadays, many surgeons are adapting this strategy.

Low-grade glioma (LGG) patients are frequently young and oligosymptomatic, usually presenting with focal seizures which can be easily managed by appropriate medication. In such patients the neurosurgeon’s responsibility is particularly great since the purpose of surgery is not primarily

the amelioration of symptoms. Neurosurgeons must keep this in mind before deciding on whether to operate and to what extent this should be done. On the other hand, recent studies have demonstrated that all LGGs will grow. The rate of growth has been calculated as about 4 mm/year (95 % CI: 3.8–4.4 mm, Mandonnet et al. 2003). This observation certainly questions whether a “wait-and-see” strategy is appropriate for the management of these patients if cytoreductive surgery may be considered an option. To the least, this observation cautions against just comparing one MRI with the previous one but rather suggests to use the earliest available MRI to decide whether a tumor is more or less stable or whether it is growing or changing, especially in the light of the quoad vitam prognosis of these patients. About 75 % of LGG patients die within 5–10 years after initial diagnosis (Keles et al. 2001; McGirt et al. 2008), and the prognosis of a low-grade glioma is similar to many non-glial cancers. Overall, such considerations justify active approaches in low-grade glioma therapy including cytoreductive surgery. Even though prospectively randomized studies which would unequivocally clarify the role of cytoreductive surgery in LGG patients are difficult to envision, a number of large and prospective cohort studies afford useful data on the value of cytoreductive surgery (McGirt et al. 2008; Smith et al. 2008). One such study from Norway provided additional interesting data (Jakola et al. 2013). In Norway basically two neurosurgical departments are involved in glioma care. One department favors biopsies, the other craniotomies. Patients treated in the hospital with the more aggressive approach survived longer. Of note: Even though controlled trials are still miss-

ing (Veeravagu et al. 2013), several large cohort studies indicate that resection should extend as far as possible because only complete or nearly complete resections, as measured by MRI as the best available imaging instrument, will have an impact on prognosis (McGirt et al. 2008; Smith et al. 2008).

Similarly, data are available which underline the value of resection in high-grade gliomas (HGG; Laws et al. 2003). One small randomized study compared biopsies with resections in elderly (>65 years of age) HGG patients (Vuorinen et al. 2003). Patients treated by craniotomy and tumor resection survived significantly longer. Another prospectively randomized study on 5-ALA for fluorescence-guided resections (Fig. 1) was able to demonstrate that patients had prolonged progression-free survival when the extent of the resection was improved by the use of 5-ALA (Stummer et al. 2006). Similar effects were observed in a study with patients being randomized into surgery with or without intraoperative MRI (Senft et al. 2011). Authors suggest that progression-free survival was improved by the use of intraoperative MRI, albeit not significantly due to the small number of patients in this study. However, most of these studies combined resection with adjuvant radiotherapy alone, and it might be questioned whether surgery in conjunction with adjuvant radiochemotherapy according to the EORTC regime still requires maximal cytoreduction. To this end, newer studies confirm that the prognostic effect of maximum possible resection of con- trast-enhancing tumor remains unmitigated or is even boosted when patients are treated by the current standard regime, concomitant radiochemotherapy, rather than radiotherapy alone (Stummer et al. 2012; Kreth et al. 2013). Similar to the results

Fig. 1 View through the microscope, the left image shows the native surgical site of a small glioblastoma. After exogenous 5-ALA application, tumor cells will become fluorescent under ultraviolet light

(red tumor on the right image). This feature identifies the tumor cells intraoperatively and facilitates complete resection