Nicolaus Andratschke

Safety and Efficacy of Stereotactic Body Radiotherapy for Stage I Non-Small-Cell Lung Cancer in Routine Clinical Practice A Patterns-of-Care and Outcome Analysis

Introduction: To evaluate safety and efficacy of stereotactic body radiotherapy (SBRT) for stage I non–small-cell lung cancer (NSCLC) in a patterns-of-care and patterns-of-outcome analysis. Methods: The working group “Extracranial Stereotactic Radiotherapy” of the German Society for Radiation Oncology performed a retrospective multicenter analysis of practice and outcome after SBRT for stage I NSCLC. Sixteen German and Austrian centers with experience in pulmonary SBRT were asked to participate. Results: Data of 582 patients treated at 13 institutions between 1998 and 2011 were collected; all institutions, except one, were academic hospitals. A time trend to more advanced radiotherapy technologies and escalated irradiation doses was observed, but patient characteristics (age, performance status, pulmonary function) remained stable over time. Interinstitutional variability was substantial in all treatment characteristics but not in patient characteristics. After an average follow-up of 21 months, 3-year freedom from local progression (FFLP) and overall survival (OS) were 79.6% and 47.1%, respectively. The biological effective dose was the most significant factor influencing FFLP and OS: after more than 106 Gy biological effective dose as planning target volume encompassing dose (N = 164), 3-year FFLP and OS were 92.5% and 62.2%, respectively. No evidence of a learning curve or improvement of results with larger SBRT experience and implementation of new radiotherapy technologies was observed. Conclusion: SBRT for stage I NSCLC was safe and effective in this multi-institutional, academic environment, despite considerable interinstitutional variability and time trends in SBRT practice. Radiotherapy dose was identified as a major treatment factor influencing local tumor control and OS.

Stereotactic radiotherapy of histologically proven inoperable stage I non-small cell lung cancer: patterns of failure.

BACKGROUND AND PURPOSE To report patterns of failure of stereotactic body radiation therapy (SBRT) in inoperable patients with histologically confirmed stage I NSCLC. MATERIALS AND METHODS Ninety-two inoperable patients (median age: 75 years) with clinically staged, histologically proven T1 (n=31) or T2 (n=61), N0, M0 non-small cell lung cancer (NSCLC) were included in this study. Treatment consisted of 3-5 fractions with 7-15 Gy per fraction prescribed to the 60% isodose. RESULTS Freedom from local recurrence at 1, 3 and 5 years was 89%, 83% and 83%, respectively. All 10 local failures were observed in patients with T2 tumors. Isolated regional recurrence was observed in 7.6%. The crude rate of distant progression was 20.7%. Overall survival at 1, 3, and 5 years was 79%, 38% and 17% with a median survival of 29 months. Disease specific survival at 1, 3, and 5 years was 93%, 64% and 48%. Karnofsky performance status, T stage, gross tumor volume and tumor location had no significant impact on overall and disease specific survival. SBRT was generally well tolerated and all patients completed therapy as planned. CONCLUSION SBRT for stage I lung cancer is very well tolerated in this patient cohort with significant cardiopulmonal comorbidity and results in excellent local control rates, although a considerable portion develops regional and distant metastases.

Pretreatment 18F-FAZA PET Predicts Success of Hypoxia-Directed Radiochemotherapy Using Tirapazamine

We evaluated the predictive value of PET using the hypoxia tracer 18F-fluoroazomycin arabinoside (18F-FAZA) for success of radiotherapy in combination with tirapazamine, a specific cytotoxin for hypoxic cells. Methods: Imaging was performed on EMT6 tumor-bearing nude mice before allocating mice into 4 groups: radiochemotherapy (RCT: 8 fractions of 4.5 Gy within 4 d combined with tirapazamine, 14 mg/kg), radiotherapy alone (RT), chemotherapy alone (tirapazamine) (CHT), or control. Treatment success was assessed by several tumor growth assays, including tumor growth time from 70 to 500 μL and absolute growth delay (aGD). The median pretreatment 18F-FAZA tumor-to-background ratio served as a discriminator between “hypoxic” and “normoxic” tumors. Results: The mean tumor growth was significantly accelerated in hypoxic control tumors (growth time from 70 to 500 μL, 11.0 d) compared with normoxic control tumors (growth time from 70 to 500 μL, 15.6 d). Whereas RT delayed tumor growth regardless of the level of hypoxia, an additive beneficial therapeutic effect of tirapazamine to RT was observed only in hypoxic tumors (aGD, 12.9 d) but not in normoxic tumors (aGD, 6.0 d). Conclusion: This study provides compelling evidence that hypoxia imaging using 18F-FAZA PET is able to predict the success of RCT of tumor-bearing mice using the hypoxia-activated chemotherapeutic agent tirapazamine. Pretreatment 18F-FAZA PET, therefore, offers a way for the individualization of tumor treatment involving radiation. The data suggest that by reserving hypoxia-directed therapy to tumors with high 18F-FAZA uptake, improvement of the therapeutic ratio is possible, as the therapeutic effect of tirapazamine seems to be restricted to hypoxic tumors.

Radiotherapy for High-Grade Gliomas Does Altered Fractionation Improve the Outcome?

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.

Late radiation-induced heart disease after radiotherapy. Clinical importance, radiobiological mechanisms and strategies of prevention

The clinical importance of radiation-induced heart disease, in particular in post-operative radiotherapy of breast cancer patients, has been recognised only recently. There is general agreement, that a co-ordinated research effort would be needed to explore all the potential strategies of how to reduce the late risk of radiation-induced heart disease in radiotherapy. This approach would be based, on one hand, on a comprehensive understanding of the radiobiological mechanisms of radiation-induced heart disease after radiotherapy which would require large-scale long-term animal experiments with high precision local heart irradiation. On the other hand - in close co-operation with mechanistic in vivo research studies - clinical studies in patients need to determine the influence of dose distribution in the heart on the risk of radiation-induced heart disease. The aim of these clinical studies would be to identify the critical structures within the organ which need to be spared and their radiation sensitivity as well as a potential volume and dose effect. The results of the mechanistic studies might also provide concepts of how to modify the gradual progression of radiation damage in the heart by drugs or biological molecules. The results of the studies in patients would need to also incorporate detailed dosimetric and imaging studies in order to develop early indicators of impending radiation-induced heart disease which would be a pre-condition to develop sound criteria for treatment plan optimisation.

Applicability of the linear-quadratic formalism for modeling local tumor control probability in high dose per fraction stereotactic body radiotherapy for early stage non-small cell lung cancer.

BACKGROUND AND PURPOSE To compare the linear-quadratic (LQ) and the LQ-L formalism (linear cell survival curve beyond a threshold dose dT) for modeling local tumor control probability (TCP) in stereotactic body radiotherapy (SBRT) for stage I non-small cell lung cancer (NSCLC). MATERIALS AND METHODS This study is based on 395 patients from 13 German and Austrian centers treated with SBRT for stage I NSCLC. The median number of SBRT fractions was 3 (range 1-8) and median single fraction dose was 12.5 Gy (2.9-33 Gy); dose was prescribed to the median 65% PTV encompassing isodose (60-100%). Assuming an α/β-value of 10 Gy, we modeled TCP as a sigmoid-shaped function of the biologically effective dose (BED). Models were compared using maximum likelihood ratio tests as well as Bayes factors (BFs). RESULTS There was strong evidence for a dose-response relationship in the total patient cohort (BFs>20), which was lacking in single-fraction SBRT (BFs<3). Using the PTV encompassing dose or maximum (isocentric) dose, our data indicated a LQ-L transition dose (dT) at 11 Gy (68% CI 8-14 Gy) or 22 Gy (14-42 Gy), respectively. However, the fit of the LQ-L models was not significantly better than a fit without the dT parameter (p=0.07, BF=2.1 and p=0.86, BF=0.8, respectively). Generally, isocentric doses resulted in much better dose-response relationships than PTV encompassing doses (BFs>20). CONCLUSION Our data suggest accurate modeling of local tumor control in fractionated SBRT for stage I NSCLC with the traditional LQ formalism.

Definition of stereotactic body radiotherapy: principles and practice for the treatment of stage I non-small cell lung cancer.

This report from the Stereotactic Radiotherapy Working Group of the German Society of Radiation Oncology (Deutschen Gesellschaft für Radioonkologie, DEGRO) provides a definition of stereotactic body radiotherapy (SBRT) that agrees with that of other international societies. SBRT is defined as a method of external beam radiotherapy (EBRT) that accurately delivers a high irradiation dose to an extracranial target in one or few treatment fractions. Detailed recommendations concerning the principles and practice of SBRT for early stage non-small cell lung cancer (NSCLC) are given. These cover the entire treatment process; from patient selection, staging, treatment planning and delivery to follow-up. SBRT was identified as the method of choice when compared to best supportive care (BSC), conventionally fractionated radiotherapy and radiofrequency ablation. Based on current evidence, SBRT appears to be on a par with sublobar resection and is an effective treatment option in operable patients who refuse lobectomy.ZusammenfassungDie Arbeitsgruppe „Stereotaktische Radiotherapie“ der Deutschen Gesellschaft für Radioonkologie (DEGRO) erarbeitete eine Definition der Körperstereotaxie (SBRT), die sich an vorhandene internationale Definitionen anlehnt: Die SBRT ist eine Form der perkutanen Strahlentherapie, die mit hoher Präzision eine hohe Bestrahlungsdosis in einer oder wenigen Bestrahlungsfraktionen in einem extrakraniellen Zielvolumen appliziert. Zur Praxis der SBRT beim nichtkleinzelligen Bronchialkarzinom (NSCLC) im frühen Stadium werden detaillierte Empfehlungen gegeben, die den gesamten Ablauf der Behandlung von der Indikationsstellung, Staging, Behandlungsplanung und Applikation sowie Nachsorge umfassen. Die Körperstereotaxie wurde als Methode der Wahl im Vergleich zu Best Supportive Care, zur konventionell fraktionierten Strahlentherapie sowie zur Radiofrequenzablation identifiziert. Die Ergebnisse nach SBRT und sublobärer Resektion erscheinen auf aktueller Datenbasis ebenbürtig. Die SBRT ist die Methode der Wahl, wenn Patienten einen operativen Eingriff in Form der Lappenresektion ablehnen.

Local tumor control probability modeling of primary and secondary lung tumors in stereotactic body radiotherapy

BACKGROUND AND PURPOSE To evaluate whether local tumor control probability (TCP) in stereotactic body radiotherapy (SBRT) varies between lung metastases of different primary cancer sites and between primary non-small cell lung cancer (NSCLC) and secondary lung tumors. MATERIALS AND METHODS A retrospective multi-institutional (n=22) database of 399 patients with stage I NSCLC and 397 patients with 525 lung metastases was analyzed. Irradiation doses were converted to biologically effective doses (BED). Logistic regression was used for local tumor control probability (TCP) modeling and the second-order bias corrected Akaike Information Criterion was used for model comparison. RESULTS After median follow-up of 19 months and 16 months (n.s.), local tumor control was observed in 87.7% and 86.7% of the primary and secondary lung tumors (n.s.), respectively. A strong dose-response relationship was observed in the primary NSCLC and metastatic cohort but dose-response relationships were not significantly different: the TCD90 (dose to achieve 90% TCP; BED of maximum planning target volume dose) estimates were 176 Gy (151-223) and 160 Gy (123-237) (n.s.), respectively. The dose-response relationship was not influenced by the primary cancer site within the metastatic cohort. CONCLUSIONS Dose-response relationships for local tumor control in SBRT were not different between lung metastases of various primary cancer sites and between primary NSCLC and lung metastases.

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.

Recursive partitioning analysis (RPA) Class does not predict survival in patients with four or more brain metastases

Background: We evaluated prognostic factors for survival in patients with four or more brain metastases in order to determine whether intense local treatment might be justified for some of them. If up to three brain metastases are present, surgical resection or radiosurgery are currently being considered in case of favorable prognostic factors. Patients and Methods: Retrospective intention-to-treat analysis of 113 patients who underwent whole-brain radiotherapy without surgical resection or radiosurgery at a single institution. Standard treatment was given with ten fractions of 3 Gy. Higher total doses were administered in 13% of patients. Recursive partitioning analysis (RPA) prognostic classes have been described by the Radiation Therapy Oncology Group (RTOG) in 1997 (class I: Karnofsky performance status [KPS] ≥ 70%, age ≤ 65 years, no extracranial metastases, controlled primary tumor; class III: KPS < 70%; class II: others). Results: Median number of brain metastases was six (four to 50). Most patients (69%) had extracranial metastases as well. Criteria of RPA Class I (II) were met in 4% (41%), whereas 56% had KPS < 70% and thus were grouped into class III (Tables 1 and 2). Complete or partial remission of brain metastases was found in 46% of patients who underwent computed tomography. Median survival was 4 months, 1-years survival rate 15%. Only age was a borderline significant prognostic factor in univariate analysis (≤ 50 years vs > 50 years, p = 0.05). Strong trends were found for KPS, extracranial metastases, control of the primary tumor, and breast primary tumor. Number of brain metastases, RPA class and treatment-related factors such as total dose or remission of brain metastases had no appreciable influence on survival (Figure 1). Multivariate analysis failed to identify any significant prognostic factor. Conclusions: Patients with four or more brain metastases seem to represent a group with unfavorable prognosis where remission of brain metastases or administration of more than 30 Gy were not associated with increased survival. The number of patients in RPA class I was too small to draw final conclusions. However, there was absolutely no survival difference between patients in class II (median survival 3.6 months) and III (median 4.2 months).Hintergrund: Die Prognosefaktoren für Patienten mit vier oder mehr Hirnmetastasen wurden ausgewertet, um festzulegen, ob einige dieser Patienten eine intensivierte Lokalbehandlung erhalten sollten. Bei Vorliegen von bis zu drei Hirnmetastasen wird gegenwärtig im Fall günstiger Prognoseparameter eine Resektion oder Radiochirurgie erwogen. Patienten und Methoden: Retrospektive Analyse (Intention-to-Treat) von 113 Patienten, die an einer einzigen Klinik mittels Ganzhirnbestrahlung ohne Resektion oder Radiochirurgie behandelt wurden. Die Standardtherapie erfolgte mit zehn Fraktionen von 3 Gy. 13% der Patienten erhielten eine höhere Gesamtdosis. Die Radiation Therapy Oncology Group (RTOG) publizierte 1997 einen prognostischen Score, der auf der Basis einer rekursiven Partitionierungsanalyse (RPA) ermittelt wurde. Die Kriterien für Klasse I lauten: Karnofsky-Index (KPS) ≥ 70%, Alter ≤ 65 Jahre, keine extrakraniellen Metastasen, kontrollierter Primärtumor; Klasse III: KPS < 70%; Klasse II: andere. Ergebnisse: Im Median lagen sechs Hirnmetastasen vor (vier bis 50). 69% der Patienten hatten auch extrakranielle Metastasen. Die Kriterien für Klasse I bzw. Klasse II erfüllten 4% bzw. 41%, wohingegen 56% wegen des schlechten Allgemeinzustands in Klasse III gruppiert werden (Tabellen 1 und 2). Eine komplette oder partielle Remission der Hirnmetasasen wurde bei 46% der Patienten, die computertomographisch nachuntersucht worden waren, festgestellt. Das mediane Überleben betrug 4 Monate (1-Jahres-Überlebensrate 15%). Lediglich das Alter konnte als grenzwertig signifikanter Prognosefaktor identifiziert werden (≤ 50 Jahre vs. > 50 Jahre, p = 0,05). Tendenzen ergaben sich auch für KPS, extrakranielle Metastasen, kontrollierten Primärtumor und Mammakarzinome. Die Zahl der Hirnmetastasen, RPA-Klasse, Ansprechen der Hirnmetastasen und Bestrahlungsdosis hatten keinen erkennbaren Einfluss auf das Überleben (Abbildung 1). Multivariat konnten keine signifikanten Faktoren herausgearbeitet werden. Schlussfolgerung: Patienten mit vier oder mehr Hirnmetastasen scheinen eine Subgruppe mit ungünstiger Prognose zu repräsentieren, bei denen ein Ansprechen der Metastasen oder eine höher dosierte Strahlentherapie das Überleben nicht verbesserten. Die Zahl der Patienten in RPA-Klasse I war zu gering für definitive Schlussfolgerungen. Es ergab sich keine signifikante Differenz im Überleben zwischen Klasse II und III (medianes Überleben 3,6 vs. 4,2 Monate).