Carsten Nieder

CERVICAL LYMPH NODE METASTASES FROM OCCULT SQUAMOUS CELL CARCINOMA: CUT DOWN A TREE TO GET AN APPLE?

PURPOSEnTo review the value of extended diagnostic work-up procedures and to compare the results of comprehensive or volume-restricted radiotherapy in patients presenting with cervical lymph node metastases from clinically undetectable squamous cell carcinoma.nnnMETHODS AND MATERIALSnA systematic review was undertaken of published papers up to May 2000.nnnRESULTSnPositron emission tomography (PET) has an overall staging accuracy of 69%, with a positive predictive value of 56% and negative predictive value of 86%. With negative routine clinical examination and computerized tomography (CT) or magnetic resonance imaging (MRI), PET detected primary tumors in 5-25% of patients, whereas ipsilateral tonsillectomy discovered carcinoma in about 25% of patients. Laser-induced fluorescence imaging with panendoscopy and directed biopsies showed some encouraging preliminary results and warrants further study. All together, the reported mucosal carcinoma emergence rates were 2-13% (median, 9.5%) after comprehensive radiotherapy and 5-44% (median, 8%) after unilateral neck irradiation. The corresponding nodal relapse rates were 8-45% (median, 19%) and 31-63% (median, 51.5%), and 5-year survival rates were 34-63% (median, 50%) and 22-41% (median, 36.5%), respectively. Retrospective single-institution comparisons between comprehensive and unilateral neck radiotherapy did not show apparent differences in outcome. Prognostic determinants for survival are the N stage, number of nodes, extracapsular extension, and histologic grade. No data were found to support the benefit of chemotherapy in this disease.nnnCONCLUSIONnPhysical examination, CT or MRI, and panendoscopy with biopsies remain the standard work-up for these patients. Routine use of PET or laser-induced fluorescence imaging cannot be firmly advocated based on presently available data. Although combination of nodal dissection with comprehensive radiotherapy yielded most favorable results, its impact on the quality of life should be recognized, and the confounding effects of patient selection for various treatment modalities on therapeutic outcome cannot be ruled out. A randomized trial comparing the therapeutic value of comprehensive vs. volume-limited radiotherapy is being considered.

Stereotactic hypofractionated radiotherapy in stage I (T1-2 N0 M0) non-small-cell lung cancer (NSCLC)

Stereotactic Radiotherapy has the potential to produce high local control rates with low risk of severe lung toxicity. From December 2000 to January 2006, 68 inoperable patients (median age 76 years) with stage I NSCLC received definitive hSRT. A mean total dose of 37.5 Gy (24–40 Gy; 60%-isodose) in 3–5 fractions was applied. Immobilisation was carried out by means of a vacuum couch and low pressure foil (Medical Intelligence, Schwab München, Germany). Staging procedures were thoracic and abdominal CT-scan, FDG-PET and CT or MRI of the brain in all patients. Clinical target volume was the tumor as seen in lung windowing of CT and in FDG-PET. Organ movements (6–22 mm) and patient positioning in the couch (3–12 mm) were added as safety margin for the definition of the planning target volume (PTV), that was enclosed by the 60%-isodose. We observed four (6%) local tumor recurrences, resulting in an actuarial local tumor control rate of 96%, 88% and 88% after 1, 2 and 3 year follow-up. Nineteen patients died, with eight patients due to cancer (12%), two to local tumor progression alone. Cancer-specific survival is 96%, 82% and 73% at 1, 2 and 3 years. Eleven patients died from comorbidities, making a 53% overall 3-year survival. Fifty five percent of the patients were affected by mild acute and subacute side effects, with only 3% experiencing pneumonitis III°. Late effects were pneumonitis III° in 1%, rib fractures in 3%, and benign pleural effusion in 2 patients. Hypofractionated SRT is safe even in elderly patients with stage I NSCLC and significantly reduced lung capacity. It leads to high local control rates and should be offered to patients not amenable for curative resection.

An Interindividual Comparison of O-(2- [18F]Fluoroethyl)-L-Tyrosine (FET)– and L-[Methyl-11C]Methionine (MET)–PET in Patients With Brain Gliomas and Metastases

PURPOSEnL-[methyl-(11)C]methionine (MET)-positron emission tomography (PET) has a high sensitivity and specificity for imaging of gliomas and metastatic brain tumors. The short half-life of (11)C (20 minutes) limits the use of MET-PET to institutions with onsite cyclotron. O-(2-[(18)F]fluoroethyl)-L-tyrosine (FET) is labeled with (18)F (half-life, 120 minutes) and could be used much more broadly. This study compares the uptake of FET and MET in gliomas and metastases, as well as treatment-induced changes. Furthermore, it evaluates the gross tumor volume (GTV) of gliomas defined on PET and magnetic resonance imaging (MRI).nnnMETHODS AND MATERIALSnWe examined 42 patients with pretreated gliomas (29 patients) or brain metastases (13 patients) prospectively by FET- and MET-PET on the same day. Uptake of FET and MET was quantified by standardized uptake values. Imaging contrast was assessed by calculating lesion-to-gray matter ratios. Tumor extension was quantified by contouring GTV in 17 patients with brain gliomas. Gross tumor volume on PET was compared with GTV on MRI. Sensitivity and specificity of MET- and FET-PET for differentiation of viable tumor from benign changes were evaluated by comparing the PET result with histology or clinical follow-up.nnnRESULTSnThere was a strong linear correlation between standardized uptake values calculated for both tracers in cortex and lesions: r = 0.78 (p = 0.001) and r = 0.84 (p < 0.001), respectively. Image contrast was similar for MET- and FET-PET (lesion-to-gray matter ratios of 2.36 ± 1.01 and 2.33 ± 0.77, respectively). Mean GTV in 17 glioma patients was not significantly different on MET- and FET-PET. Both MET- and FET-PET delineated tumor tissue outside of MRI changes. Both tracers provided differentiated tumor tissue and treatment-related changes with a sensitivity of 91% at a specificity of 100%.nnnCONCLUSIONSnO-(2-[(18)F]fluoroethyl)-L-tyrosine-PET and MET-PET provide comparable diagnostic information on gliomas and brain metastases. Like MET-PET, FET-PET can be used for differentiation of residual or recurrent tumor from treatment-related changes/pseudoprogression, as well as for delineation of gliomas.

IMPLICATIONS OF IMT-SPECT FOR POSTOPERATIVE RADIOTHERAPY PLANNING IN PATIENTS WITH GLIOMAS

PURPOSEnUsing MRI, residual tumor cannot be differentiated from nonspecific postoperative changes in patients with brain gliomas after surgical resection. The goal of this study was to analyze the value of 123I-alpha-methyl-tyrosine-single photon emission CT (IMT-SPECT) in radiotherapy planning of patients with brain gliomas after surgical resection.nnnMETHODS AND MATERIALSnIn 66 patients with surgically resected brain gliomas (33 glioblastomas, 20 anaplastic astrocytomas, 7 anaplastic oligodendrogliomas, and 6 low-grade astrocytomas), IMT-SPECT and MRI were performed for radiotherapy planning. On the MRI/IMT-SPECT fusion images, the volume with IMT uptake was compared with the volume of the hyperintensity areas of T(2)-weighted MRI and with the volume of contrast enhancement on T(1)-weighted MRI. The regions with IMT uptake and/or MRI changes (composite Vol-MRI/IMT), regions with overlay of IMT uptake and MRI changes (common Vol-MRI/IMT), area with IMT uptake without MRI changes (increase Vol-MRI/IMT), and area with only MRI changes (Vol-MRI minus IMT) were analyzed separately. The planning target volume and boost volume defined using MRI information alone was compared with the planning target volume and boost volume defined by also using the SPECT information.nnnRESULTSnFocally increased IMT uptake was observed in 25 (38%) of 66 patients, contrast enhancement on MRI was outlined in 59 (89%) of 66 patients, and hyperintensity areas on T(2)-weighted MRI were found in all 66 investigated patients. The mean composite Vol-T(2)/IMT was 73 cm(3). The relative increase Vol-T(2)/IMT, mean relative common Vol-T(2)/IMT, and mean relative Vol-T(2) minus IMT was 4%, 6%, and 90% of the composite Vol-T(2)/IMT, respectively. The mean composite Vol-T(1)/IMT was 14 cm(3) and the mean relative increase Vol-T(1)/IMT, mean relative common Vol-T(1)/IMT, and mean relative Vol-T(1) minus IMT was 21%, 4%, and 64% of the mean composite Vol-T(1)/IMT, respectively. In 19 (29%) of 66 patients, the focal IMT uptake was located outside the MRI changes. In this subgroup, the mean residual volume defined by focal IMT uptake in MRI/IMT-SPECT images, mean Vol-T(1), and mean Vol-T(2) was 19 cm(3), 10 cm(3), and 70 cm(3), respectively. The mean relative increase T(2)/IMT was 14% and T(1)/IMT was 61%. In this subgroup, the additional information of SPECT led to an increase in boost volume (mean relative increase BV-IMT) by 20%.nnnCONCLUSIONnIn patients with surgically resected brain gliomas, the size and location of residual IMT uptake differs considerably from the abnormalities found on postoperative MRI. Because of the known high specificity of IMT uptake for tumor tissue, the findings on IMT-SPECT may significantly modify the target volumes for radiotherapy planning. This will help to focus the high irradiation dose on the tumor area and to spare normal brain tissue.

Radiotherapy for High-Grade Gliomas

Background and Purpose:The publication of Radiation Therapy Oncology Group (RTOG) Study 83-02 in 1996 stimulated further investigations of altered fractionation, i. e., application of more than one fraction per day, in high-grade gliomas. This review summarizes the results of trials published between January 1997 and June 2002.Material and Methods:To identify suitable trials, a Medline search was performed by use of the following key words: brain tumors/astrocytoma/glioma/high-grade glioma/malignant glioma/glioblastoma multiforme and accelerated radiotherapy/hyperfractionated radiotherapy/altered fractionation. In addition, the search was extended to reference lists of articles and textbooks. Whenever possible, data were extracted from the original papers on an intention-to-treat basis, i. e., patients with protocol violations were not excluded for the purpose of this analysis. Studies in brain stem gliomas, pediatric patients and studies which achieved acceleration by radiosurgery, stereotactic radiotherapy, or brachytherapy rather than conventional external-beam treatment were not included. An exploratory analysis of 2-year survival was also performed. For this purpose, the 2-year survival rate was extracted from each individual study. The total number of 2-year survivors was then calculated for each treatment strategy and compared by use of the χ2-test.Results:The authors identified 1,414 patients from 21 studies; two of these were randomized phase III studies. In seven studies (658 patients), chemotherapy or radiosensitizers were not administered in addition to radiotherapy. The others provide a very heterogeneous set of data, because a large variety of drugs and administration schedules was used. Seven studies included patients with glioblastoma multiforme only, two were limited to patients with anaplastic gliomas. Dose per fraction was 1.2–1.8 Gy in 17 studies and 1.9–2.65 Gy in four. Overall treatment time was 12–31 days, except for one study. Three out of five studies where three fractions per day were administered, included a 2-week break (split-course studies). None of the studies reported a significant improvement in survival by altered fractionation in comparison to either institutional historical controls or their respective randomized control arm. Doses of 60–70 Gy do not appear to improve survival compared to 50–60 Gy. The current data provide no arguments for use of three instead of two fractions per day. Median survival was 10 months after radiotherapy alone (658 patients) and 11 months after combined treatment (756 patients). Regarding 2-year survival rates, radiotherapy alone resulted in 13%, combined chemoradiation or use of sensitizers in 23% (p < 0.0001). However, prognostic factors such as tumor histology were not equally distributed and favor the combined-treatment group. Evaluation of six studies of conventional radiotherapy alone resulted in data from 571 patients. Their median survival was 10.8 months. Cumulative 2-year survival amounted to 15%. The studies of conventional radiotherapy plus chemotherapy or sensitizers included 1,115 patients with a median survival of 11 months (2-year survival rate 18.5%).Conclusion:Altered fractionation shortens the overall treatment time for adult patients with supratentorial high-grade gliomas. However, there is no significant survival improvement.Hintergrund und Ziel:Die Publikation der RTOG-Studie 83-02 im Jahre 1996 führte zu einem gesteigerten Interesse an der Überprüfung unkonventioneller Fraktionierungsschemata, bei denen mehr als eine Fraktion pro Tag gegeben wird. Dieser Übersichtsartikel fasst die Ergebnisse solcher Behandlungen in Studien, die zwischen Januar 1997 und Juni 2002 publiziert wurden, zusammen.Material und Methodik:Um entsprechende Studien zu identifizieren, erfolgte eine Medline-Suche mit folgenden Schlüsselwörtern: brain tumors/astrocytoma/glioma/high-grade glioma/malignant glioma/glioblastoma multiforme und accelerated radiotherapy/hyperfractionated radiotherapy/altered fractionation. Zusätzlich wurde im Literaturverzeichnis der Artikel und von Lehrbüchern gesucht. Wenn möglich, wurden die Daten aus den Originalarbeiten im Sinne einer Intention-to-treat-Analyse extrahiert, d. h., Patienten mit Protokollverletzungen wurden für diese Auswertung nicht ausgeschlossen. Studien zu Hirnstammgliomen, pädiatrische Serien und Studien, die durch Radiochirurgie, stereotaktische Strahlentherapie oder Brachytherapie anstelle von konventioneller perkutaner Strahlentherapie akzelerierten, wurden nicht eingeschlossen. Im Sinne einer explorativen Analyse wurden zusätzlich die 2-Jahres-Überlebensraten der einzelnen Studien bestimmt. Die Gesamtzahl der 2-Jahres-Überlebenden für die verschiedenen Therapieansätze wurde errechnet und mittels χ2-Test verglichen.Ergebnisse:Die Autoren identifizierten 1 414 Patienten in 21 Studien, darunter zwei randomisierte Phase-III-Studien. In sieben Studien (658 Patienten) wurden weder Chemotherapie noch radiosensibilisierende Substanzen zusätzlich zur Bestrahlung verwendet. Die anderen Studien sind sehr heterogen, da eine Vielzahl von Medikamenten und Applikationsschemata benutzt wurde. Sieben Studien schlossen nur Patienten mit Glioblastoma multiforme ein, zwei nur Patienten mit anaplastischen Gliomen. Die Dosis pro Fraktion betrug in 17 Studien 1,2–1,8 Gy und in vier Studien 1,9–2,65 Gy. Die Gesamtbehandlungszeit lag außer in einer Studie bei 12–31 Tagen. Von fünf Studien, in denen drei Fraktionen pro Tag gegeben wurden, wiesen drei eine 2-wöchige Behandlungspause auf („split course“). In keiner der Studien mit eigenem historischen Kontrollarm oder randomisiertem Kontrollarm ergab sich durch eine Modifikation der Fraktionierung ein signifikanter Überlebensvorteil. Dosen zwischen 60 und 70 Gy führten im Vergleich zu 50–60 Gy nicht zu einem verbesserten Überleben. Die vorliegenden Daten liefern keine Argumente für die Applikation von drei Fraktionen pro Tag. Das mediane Überleben betrug 10 Monate nach alleiniger Strahlentherapie (658 Patienten) und 11 Monate nach kombinierter Behandlung (756 Patienten). Die alleinige Bestrahlung führte zu einer 2-Jahres-Überlebensrate von 13%, die kombinierte Radiochemotherapie oder die Gabe sensibilisierender Substanzen zu 23% (p < 0,0001). Allerdings waren die prognostischen Faktoren, wie z.B. Tumorhistologie, nicht gleich verteilt, sondern in den kombiniert behandelten Kollektiven günstiger. Die Auswertung von sechs Studien mit konventionell fraktionierter Strahlentherapie ergab Vergleichsdaten von 571 Patienten. Deren medianes Überleben betrug 10,8 Monate. Die 2-Jahres-Überlebensrate lag bei 15%. Die Studien zur konventionellen Strahlentherapie plus Chemotherapie oder Radiosensibilisierung schlossen 1 115 Patienten ein (medianes Überleben 11 Monate, 2-Jahres-Überlebensrate 18,5%).Schlussfolgerung:Die modifizierte Fraktionierung verkürzt die Gesamtbehandlungszeit erwachsener Patienten mit supratentoriellen hochgradigen Gliomen. Aus dieser Strategie ergibt sich jedoch kein signifikanter Überlebensvorteil.

The Impact of Tumor Biology on Cancer Treatment and Multidisciplinary Strategies

Tumorigenesis.- Tumor Growth and Cell Proliferation.- Angiogenesis.- Tumor Physiology (Phenomenology).- Adhesion, Invasion, Integrins and Beyond.- Development of Metastases.- Role of the Immune System in Cancer Development and Therapeutic Implications.- Cancer Prevention .- Tumor Detection by Morphological and Biological Imaging.- Tumor Detection by Biological Markers (Serum, Urine, Breathing Gas, Proteomics).- Quantitative Cell Kill by Chemo- and Radiotherapy.- Impact of Molecularly Targeted Agents on Cell Kill in Bi- or Trimodal Approaches (i.e. plus Chemo, Radio-, or Radiochemotherapy).- Translational Studies for Target-Based Drugs.- Molecular Mechanisms of Treatment Resistance.- Physiological Mechanisms of Treatment Resistance.- Influence of Repopulation on Treatment Resistance.- Molecular Tools, Gene Expression Profiling.- Strategies of Gene Transfer/Silencing and Technical Considerations.- Tumor Biologys Impact on Clinical Cure Rates.- Can Dose-Escalated Radiotherapy Eventually Cure All Biologically Distinct Subsets of a Certain Tumor Type? Answers from Stereotactic Lung and Liver Radiotherapy Experience.-Low-Dose Radiotherapy - A Chemopotentiator?.- Treatment of the Primary Tumor in Metastatic Cancer: Influence on Outcome.- Subject Index.- List of Contributors.

Immunohistochemically detected p53 mutations in epithelial tumors and results of treatment with chemotherapy and radiotherapy. A treatment-specific overview of the clinical data.

Background: The aim was to ascertain whether many hundreds of clinical reports over the last decade are consistent with the prediction of a poorer outcome in cancer patients wit p53 abnormalities treated with cytotoxic drugs and radiation.nn Material and Methods: There are 301 studies on the influence of p53 overexpression published through summer 2000, in which chemotherapy or radiotherapy was used alone or in combination with surgery. From 45 reports meeting stringent selection rules, comparison groups are identified in whom the same measure of outcome was reported for the same treatment applied to the same tumor, with results corrected for important prognostic factors. Metaanalysis techniques are then applied to the comparison groups. Attention was limited to reports using immunohistochemical techniques, to form comparison groups of sufficient size.nn Results: Four comparison groups were identified by treatment and endpoint: 1) Stage I–III breast cancer (surgery and chemotherapy, disease-free survival, seven studies); 2) stage I–III breast cancer (surgery and chemotherapy, overall survival, six studies); 3) stage II–IV head and neck cancer (radiotherapy and chemotherapy, overall survival, five studies); 4) FIGO I–IV ovarian cancer (surgery and chemotherapy, overall survival, six studies). In the breast (disease-free survival) and ovarian (overall survival) comparison groups, the hazard ratio for a deleterious effect of p53 overexpression was significant or marginally significant, depending on assumed ranges for unreported hazard ratios in non-significant studies.nn Conclusions: Despite the many caveats related to metaanalysis applied to retrospective data, high variability of immunohistochemical technique, etc., a nearly significant negative effect of p53 overexpression on outcome of treatment with cytotoxic drugs and radiation emerges in the few studies where heterogeneity can be sufficiently reduced or accounted for.Hintergrund: Es sollte überprüft werden, ob die im letzten Jahrzehnt zahlreich publizierten klinischen Untersuchungen die Aussage zulassen, dass eine Chemo- und Strahlentherapie mit einem schlechteren Ergebnis bei der Therapie von Tumorpatienten einhergeht bei Vorliegen einer p53-Mutation.nn Material und Methode: Bis Sommer 2000 wurden 301 Studien zum Einfluss einer p53-Überexpression publiziert, bei denen eine Chemo- bzw. Strahlentherapie allein oder in Kombination mit einer Operation eingesetzt wurde. Von 45 Studien, die definierte Selektionskriterien enthielten, wurden Untergruppen gebildet, bei denen der gleiche klinische Endpunkt bei Vergleichbarkeit von Behandlung und Tumorstadium unter Berücksichtigung wichtiger prognostischer Parameter auf das Behandlungsergebnis erfasst wurde. Diese Untergruppen wurden einer Metaanalyse unterzogen. Um dabei eine ausreichende Gruppengröße zu gewährleisten, wurde die Auswahl der Studien auf solche mit immunhistochemischer Untersuchung des p53-Status begrenzt.nn Ergebnisse: Vier Untergruppen konnten gemäß Behandlung und Endpunkt identifiziert werden: 1. Stadium-I-III-Mammakarzinome (Operation und Chemotherapie, krankheitsfreies Überleben, sieben Studien), 2. Stadium-I-III-Mammakarzinome (Operation und Chemotherapie, Gesamtüberleben, sechs Studien), 3. Stadium-II-IV-Kopf-Hals-Tumoren (Radiotherapie und Chemotherapie, Gesamtüberleben, fünf Studien) und 4. FIGO-Stadien-I-IV-Ovarialkarzinome (Operation und Chemotherapie, Gesamtüberleben, sechs Studien). Für die Gruppen Mamma- (krankheitsfreies Überleben) und Ovarialkarzinome (Gesamtüberleben) fand sich eine signifikante bzw. marginal signifikante Hazard Ratio für einen negativen Einfluss einer p53-Überexpression auf das Behandlungsergebnis, wobei Spannweiten für nicht publizierte Hazard Ratios in den nicht signifikanten Studien geschätzt wurden.nn Schlussfolgerung: Ungeachtet der vielen Einschränkungen, die bei der Metaanalyse der retrospektiven Daten bei ausgeprägter Variabilität der immunhistochemisch eingesetzten Techniken u.a. zu berücksichtigen sind, lässt sich ein nahezu signifikant negativer Effekt einer p53-Überexpression auf das Behandlungsergebnis nachweisen, wenn die Heterogenität ausreichend reduziert bzw. berücksichtigt wird.

Influence of differing radiotherapy strategies on treatment results in diffuse large-cell lymphoma: a review

In the absence of evidence from randomised trials, radiation treatment of diffuse large-cell lymphoma of B-cell type represents an area of controversy with considerable differences in patterns of practice. The present literature survey aims at clarification of the role of radiotherapy in combined modality settings by identification of dose-response relationships, predictive factors for local control, and potential pitfalls in the interpretation of retrospective studies. Radiotherapy might increase local control in initially involved areas and is usually delivered to these sites (involved-field treatment). Combined modality treatment is currently recommended for patients in stage I or II if they are not treated in the context of prospective studies. Whether involved-field consolidation radiotherapy after systemic treatment in patients with bulky, stage III-IV lymphomas should be routinely recommended is presently unclear. Definition of bulky disease is arbitrary and varied between 6 and 10cm, reflecting a considerable difference in the number of clonogenic tumour cells. Several retrospective and one prospective randomised study suggest improved disease-free and overall survival by radiotherapy in advanced stages. The 5-year local control by radiotherapy was 93-98%. Currently, we recommend the following minimum doses for involved-field radiotherapy derived from this literature survey. Lymphomas with initial size <3.5 cm (possibly <6 cm) can be treated with 30 or 30.6Gy when a complete remission (CR) has been achieved by chemotherapy. The next group might be sufficiently controlled by 36Gy, but it remains unclear whether the cut-off should be 6cm or higher. Forty Gy appears to control tumours in the range of 7-10cm. Most likely, 45Gy does not have to be exceeded for larger lesions. Data on those with less than CR are contradictory. Judging the amount of viable tumour in these patients is problematic, but crucial to determine the intensity of further treatment. The value of positron emission tomography is still under investigation. Because the difference between doses of 30 and 40Gy might actually make a difference for the long-term toxicity of radiotherapy in some of the normal tissues and organs at risk (salivary glands, orbital structures, lung, heart, etc.), it appears prudent to resolve the open questions in prospective trials with careful documentation of side effects.

High-Precision Radiation Therapy with Integrated Biological Imaging and Tumor Monitoring

Purpose:To describe an emerging concept of high-precision radiotherapy, a modality characterized by adaptation to patient and organ movements, which might occur between fractions or even during radiation delivery.Methods and Results:Today’s unprecedented technical capabilities to visualize the target volume and create conformal dose distributions allow for avoidance of critical structures or targeted treatment intensification within a conventionally imaged, anatomically defined tumor. The success of selective dose escalation depends on (1) correct staging and target volume identification, which can be improved by biological imaging, and (2) identification of biologically relevant subvolumes, which determine tumor control. Current efforts are directed at different methods, such as positron emission tomography and magnetic resonance spectroscopy, and integrating them into treatment planning.Conclusion:Early clinical trials assessing the safety and efficacy of image- and biology-guided radiotherapy are ongoing. The same modalities might be used to determine the individual tumor response during treatment and to adapt therapy. Temporal changes in tumor biology, which might represent both a challenge and a chance with regard to adaptation of treatment, need to be addressed in greater detail.Ziel:Beschreibung eines in der Entwicklung befindlichen Konzepts zur Hochpräzisionsbestrahlung, einer Behandlungsmodalität, welche die Lagevariabilität des Patienten und die Organbeweglichkeit zwischen den einzelnen Fraktionen und während einer Einzelfraktion berücksichtigt. Methodik und Ergebnisse:Die aktuellen Techniken zur Darstellung des Zielvolumens und zur Berechnung konformaler Dosisverteilungen ermöglichen die Schonung kritischer Strukturen oder die gezielte Intensivierung der Behandlung innerhalb eines konventionell anatomisch definierten Zielvolumens. Der Erfolg einer selektiven Dosiseskalation hängt 1. vom korrekten Staging und von der Festlegung des Zielvolumens, die durch biologische Bildgebung verbessert werden, und 2. von der tatsächliche Darstellung biologisch relevanter Tumorsubvolumina, welche die Tumorkontrollwahrscheinlichkeit bestimmen, ab (Abbildung 1). Gegenwärtig werden verschiedene Methoden in die Bestrahlungsplanung einbezogen, z. B. Positronenemissionstomographie und Magnetresonanzspektroskopie.Schlussfolgerung:Klinische Pilotstudien zur Bewertung der Sicherheit und Effektivität dieser Therapie haben begonnen. Außerdem können dieselben Methoden das individuelle Ansprechen von Tumoren im Verlauf der Behandlung erfassen und dadurch Änderungen begründen. Die zeitlichen Veränderungen der Tumorbiologie (Abbildung 2) müssen aber noch detaillierter untersucht werden, da sie sowohl eine Herausforderung als auch eine Chance bezüglich der Behandlungsanpassung sein können (Abbildung 3).

Stereotactic fractionated radiotherapy for recurrent capillary hemangioma of the cavernous sinus.

Background and Purpose:Capillary hemangioma of the cavernous sinus is a rare benign skull base tumor that can successfully be treated with radiotherapy. Due to its location, both the tumor itself and the treatment might cause significant functional deficits. Therefore, the different treatment options should be discussed with the patients.Case Report:A case of successful stereotactic fractionated radiotherapy (SFRT) performed after multiple recurrences is described. A 62-year-old male patient with a hemangioma of the right cavernous sinus, orbita and suprasellar region who had previously undergone three surgical procedures received postoperative SFRT for the residual tumor (target volume 85 cm3, Figure 1). SFRT was administered 5 months after surgery with single daily fractions of 2 Gy to a total dose of 40 Gy.Results:No acute or late toxicity of SFRT was observed. Symptomatic improvement was evident 6 months after SFRT. Imaging over a 20-month period showed a continuous and pronounced decrease in residual tumor size (Figure 2).Conclusion:Postoperative SFRT with moderate doses is well tolerated and might induce both symptomatic and radiologic improvement of large capillary hemangioma.Hintergrund und Ziel:Das kapilläre Hämangiom des Sinus cavernosus ist ein seltener gutartiger Schädelbasistumor, der erfolgreich mittels Bestrahlung behandelt werden kann. Lokalisationsbedingt kann sowohl der Tumor selbst als auch seine Behandlung signifikante funktionelle Beeinträchtigungen hervorrufen. Daher sollten die unterschiedlichen Behandlungsmöglichkeiten mit den Patienten diskutiert werden.Fallbericht:Beschrieben wird der Fall einer erfolgreichen stereotaktischen fraktionierten Strahlentherapie (SFRT) nach mehrfachen Rezidiven. Ein 62-jähriger Patient mit einem Hämangiom des rechten Sinus cavernosus, der Orbita und der suprasellären Region, der zuvor dreimal operiert worden war, erhielt eine postoperative SFRT des Resttumors (Zielvolumen 85 cm3, Abbildung 1). Die SFRT erfolgte 5 Monate nach dem letzten Eingriff mit einer täglichen Einzeldosis von 2 Gy bis insgesamt 40 Gy.Ergebnisse:Die SFRT führte nicht zu akuten oder verzögerten Nebenwirkungen. Eine Besserung der Beschwerden stellte sich 6 Monate nach der SFRT ein. Die Bildgebung über bisher 20 Monate zeigte eine kontinuierliche und deutliche Größenreduktion des Resttumors (Abbildung 2).Schlussfolgerung:Eine postoperative SFRT mit moderaten Dosen ist gut verträglich und kann sowohl eine symptomatische als auch eine bildgebende Verbesserung bei großen kapillären Hämangiomen herbeiführen.