Background: Advancement in diagnosis and treatment of various cancer entities led to an increasing incidence of brain metastases in the last decades. Surgical excision of single and multiple brain metastases is one of the central treatment options beside radiotherapy, radiosurgery and chemotherapy. To evaluate the benefit of surgery with/without whole-brain radiation therapy (WBRT) in single brain metastases and the influence of image guidance for brain metastases resection, 104 patients were retrospectively evaluated for post-operative outcome. Patients and Methods: Between January 1994 and December 1999 150 patients were surgically treated for brain metastases at the Department of Neurosurgery at the Technical University of Dresden. Outcome could be evaluated in 104 patients with respect to special treatment strategies and survival time (69 patients with single and 35 patients with multiple lesions). Results: Most metastases originated from primary lung and breast tumours. Karnofsky performance score improved on average by 10 after surgery. The extent of the extracerebral tumour burden was the main influence on survival time. Patients’ age below 70 years was combined with prolonged survival time (median survival time, MST: 4.5 months vs. 7 months). Patients with solitary cerebral metastasis had a MST of 16 months, whereas patients with singular lesions had a MST of 7 and 4 months, depending on the extent of the extracerebral tumour growth. Additional post-operative WBRT with 30 Gy was combined with an increase in MST in patients with single brain metastasis (surgery + WBRT: MST 13 months; surgery only: MST 8 months). In addition, the rate of recurrent cerebral tumour growth was distinctly higher in the non-WBRT group. Neuronavigation did not significantly improve post-operative survival time. In 80% of patients extracerebral tumour growth limited patients’ survival. Conclusion: Surgery is an initial treatment option in patients with single and multiple brain metastases especially with large tumours (> 3 cm). Post-operative WBRT seems to prolong survival time in patients with single brain metastasis by decreasing local and distant tumour recurrence. Neuronavigational devices permit a targeted approach. Multiple processes can be extirpated in one session without prolonging the hospitalisation time for the patient. However, neuronavigational devices cannot assure complete tumour resection. / Hintergrund: Fortschritte in der Diagnostik und Therapie von Krebserkrankungen haben in den letzten Jahrzehnten zu einer steigenden Inzidenz von Hirnmetastasen geführt. Die chirurgische Entfernung singulärer und multipler Hirnmetastasen stellt neben Strahlentherapie, Radiochirurgie und Chemotherapie eine zentrale Therapieoption dar. Um die Wertigkeit der chirurgischen Behandlung von singulären Hirnmetastasen mit/ohne Ganzhirnbestrahlung (WBRT) und den Einfluss der Neuronavigation zu untersuchen, wurden 104 Patienten retrospektiv bezüglich ihres postoperativen «Outcomes» untersucht. Patienten und Methoden: Zwischen Januar 1994 und Dezember 1999 wurden 150 Patienten mit Hirnmetastasen in der Klinik für Neurochirurgie der Technischen Universität Dresden operiert. Das «Outcome » von 104 Patienten konnte bezüglich der verschiedenen Behandlungsstrategien und Überlebenszeit ausgewertet werden (69 Patienten mit singulären und 35 Patienten mit multiplen Läsionen). Ergebnisse: Die meisten Metastasen stammen von Lungen- und Mammakarzinomen. Nach operativer Behandlung verbesserte sich der Karnofsky-Index um durchschnittlich 10. Das Ausmaß der extrazerebralen Tumormasse stellte die Haupteinflussgröße für die Überlebenszeit dar. Ein Lebensalter unter 70 Jahren war mit einer verlängerten Überlebenszeit verbunden (mittlere Überlebenszeit, MÜZ: 4,5 Monate vs. 7 Monate). Patienten mit solitären Metastasen hatten eine MÜZ von 16 Monaten, während Patienten mit singulären Läsionen, abhängig vom Ausmaß des extrazerebralen Tumorwachstums, eine MÜZ von 7 bzw. 4 Monaten aufweisen. Eine zusätzliche postoperative WBRT mit 30 Gy zeigte eine Verbesserung der MÜZ bei Patienten mit singulären Hirnmetastasen (OP + WBRT: MÜZ 13 Monate; OP allein: MÜZ 8 Monate). Gleichzeitig war die Rate der zerebralen Tumorrezidive in der Nicht-WBRT Gruppe deutlich höher. Die postoperative Überlebenszeit wurde durch Verwendung der Neuronavigation nicht signifikant verbessert. In 80% der Patienten limitierte das extrazerebrale Tumorwachstum die Überlebenszeit. Fazit: Bei Patienten mit singulären und multiplen Metastasen stellt die initiale chirurgische Tumorentfernung eine Therapiealternative insbesondere bei großen Tumoren (> 3 cm) dar. Eine postoperative WBRT scheint die ÜLZ der Patienten mit singulären Hirnmetastasen durch Begrenzung des Auftretens von Rezidivtumoren zu verlängern. Die Neuronavigation erlaubt eine gezielte Zugangsplanung. Multiple Prozesse können einzeitig operiert werden, ohne dass die postoperative stationäre Verweildauer verlängert wird. Hingegen wird eine radikale Tumorentfernung durch Verwendung der Neuronavigation nicht gewährleistet. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

Background: Advancement in diagnosis and treatment of various cancer entities led to an increasing incidence of brain metastases in the last decades. Surgical excision of single and multiple brain metastases is one of the central treatment options beside radiotherapy, radiosurgery and chemotherapy. To evaluate the benefit of surgery with/without whole-brain radiation therapy (WBRT) in single brain metastases and the influence of image guidance for brain metastases resection, 104 patients were retrospectively evaluated for post-operative outcome. Patients and Methods: Between January 1994 and December 1999 150 patients were surgically treated for brain metastases at the Department of Neurosurgery at the Technical University of Dresden. Outcome could be evaluated in 104 patients with respect to special treatment strategies and survival time (69 patients with single and 35 patients with multiple lesions). Results: Most metastases originated from primary lung and breast tumours. Karnofsky performance score improved on average by 10 after surgery. The extent of the extracerebral tumour burden was the main influence on survival time. Patients’ age below 70 years was combined with prolonged survival time (median survival time, MST: 4.5 months vs. 7 months). Patients with solitary cerebral metastasis had a MST of 16 months, whereas patients with singular lesions had a MST of 7 and 4 months, depending on the extent of the extracerebral tumour growth. Additional post-operative WBRT with 30 Gy was combined with an increase in MST in patients with single brain metastasis (surgery + WBRT: MST 13 months; surgery only: MST 8 months). In addition, the rate of recurrent cerebral tumour growth was distinctly higher in the non-WBRT group. Neuronavigation did not significantly improve post-operative survival time. In 80% of patients extracerebral tumour growth limited patients’ survival. Conclusion: Surgery is an initial treatment option in patients with single and multiple brain metastases especially with large tumours (> 3 cm). Post-operative WBRT seems to prolong survival time in patients with single brain metastasis by decreasing local and distant tumour recurrence. Neuronavigational devices permit a targeted approach. Multiple processes can be extirpated in one session without prolonging the hospitalisation time for the patient. However, neuronavigational devices cannot assure complete tumour resection. / Hintergrund: Fortschritte in der Diagnostik und Therapie von Krebserkrankungen haben in den letzten Jahrzehnten zu einer steigenden Inzidenz von Hirnmetastasen geführt. Die chirurgische Entfernung singulärer und multipler Hirnmetastasen stellt neben Strahlentherapie, Radiochirurgie und Chemotherapie eine zentrale Therapieoption dar. Um die Wertigkeit der chirurgischen Behandlung von singulären Hirnmetastasen mit/ohne Ganzhirnbestrahlung (WBRT) und den Einfluss der Neuronavigation zu untersuchen, wurden 104 Patienten retrospektiv bezüglich ihres postoperativen «Outcomes» untersucht. Patienten und Methoden: Zwischen Januar 1994 und Dezember 1999 wurden 150 Patienten mit Hirnmetastasen in der Klinik für Neurochirurgie der Technischen Universität Dresden operiert. Das «Outcome » von 104 Patienten konnte bezüglich der verschiedenen Behandlungsstrategien und Überlebenszeit ausgewertet werden (69 Patienten mit singulären und 35 Patienten mit multiplen Läsionen). Ergebnisse: Die meisten Metastasen stammen von Lungen- und Mammakarzinomen. Nach operativer Behandlung verbesserte sich der Karnofsky-Index um durchschnittlich 10. Das Ausmaß der extrazerebralen Tumormasse stellte die Haupteinflussgröße für die Überlebenszeit dar. Ein Lebensalter unter 70 Jahren war mit einer verlängerten Überlebenszeit verbunden (mittlere Überlebenszeit, MÜZ: 4,5 Monate vs. 7 Monate). Patienten mit solitären Metastasen hatten eine MÜZ von 16 Monaten, während Patienten mit singulären Läsionen, abhängig vom Ausmaß des extrazerebralen Tumorwachstums, eine MÜZ von 7 bzw. 4 Monaten aufweisen. Eine zusätzliche postoperative WBRT mit 30 Gy zeigte eine Verbesserung der MÜZ bei Patienten mit singulären Hirnmetastasen (OP + WBRT: MÜZ 13 Monate; OP allein: MÜZ 8 Monate). Gleichzeitig war die Rate der zerebralen Tumorrezidive in der Nicht-WBRT Gruppe deutlich höher. Die postoperative Überlebenszeit wurde durch Verwendung der Neuronavigation nicht signifikant verbessert. In 80% der Patienten limitierte das extrazerebrale Tumorwachstum die Überlebenszeit. Fazit: Bei Patienten mit singulären und multiplen Metastasen stellt die initiale chirurgische Tumorentfernung eine Therapiealternative insbesondere bei großen Tumoren (> 3 cm) dar. Eine postoperative WBRT scheint die ÜLZ der Patienten mit singulären Hirnmetastasen durch Begrenzung des Auftretens von Rezidivtumoren zu verlängern. Die Neuronavigation erlaubt eine gezielte Zugangsplanung. Multiple Prozesse können einzeitig operiert werden, ohne dass die postoperative stationäre Verweildauer verlängert wird. Hingegen wird eine radikale Tumorentfernung durch Verwendung der Neuronavigation nicht gewährleistet. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

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INTRODUÇÃO: Os tumores da cavidade oral localmente avançados são neoplasias agressivas e com alto risco de recaída após o tratamento radical definitivo. O presente estudo foi realizado para avaliar a eficácia e segurança da quimioterapia de indução antes da cirurgia em pacientes com câncer de cavidade oral. MÉTODOS: Uma revisão sistemática da literatura foi realizada e apenas ensaios clínicos randomizados prospectivos fase III que comparavam a quimioterapia de indução seguida de cirurgia com ou sem radioterapia pósoperatória (Grupo QT) à cirurgia com ou sem radioterapia pós-operatória (Grupo Controle) foram elegíveis. Dois autores selecionaram os estudos de forma independente, respeitando os critérios de elegibilidade preestabelecidos. Avaliou-se também o risco de viés dos estudos incluídos. RESULTADOS: No total, dois estudos foram selecionados. Quatrocentos e cinquenta e um pacientes foram aleatoriamente randomizados para o Grupo QT (n = 226) e para o Grupo Controle (n = 225). A maioria dos pacientes tinha tumores em estádios clínicos III/IV (89,1%). Ambos os estudos foram classificados como tendo baixo risco de viés. Nenhum benefício estatisticamente significante em favor da quimioterapia de indução foi encontrado quanto à recorrência locorregional, à sobrevida livre de doença e à sobrevida global. A análise de subgrupo com dados individuais dos pacientes com doença cervical linfonodal N2 demonstrou benefício estatisticamente significante em sobrevida global no grupo que recebeu quimioterapia de indução. Nenhuma análise estatística foi realizada em relação à segurança das estratégias de tratamento, uma vez que os estudos incluídos não avaliaram diretamente esse desfecho. CONCLUSÕES: Com base nos estudos disponíveis, a quimioterapia de indução não melhora os resultados clínicos em pacientes com câncer de cavidade oral quando administrada antes da cirurgia radical com intenção curativa. O subgrupo de pacientes com doença linfonodal cervical N2 é aquele que eventualmente poderia se beneficiar da estratégia de quimioterapia de indução / INTRODUCTION: Locoregionally advanced oral cavity cancers are aggressive tumors with high risk of relapse after definitive treatment. This study was performed to assess the effectiveness and safety of induction chemotherapy prior to surgery for untreated oral cavity cancer patients. METHODS: Only prospective phase III randomized studies comparing induction chemotherapy followed by surgery with or without postoperative radiotherapy (Chemo Group) compared with surgery with or without postoperative radiotherapy (Control Group) were eligible. Two of the authors independently selected and assessed the studies regarding eligibility criteria and risk of bias. RESULTS: Two studies were selected. A total of 451 patients were randomly assigned to Chemo Group (n = 226) versus Control Group (n = 225). Most patients had tumors at clinical stages III/IV (89.1%). Both trials were classified as having low risk of bias. No significant overall benefit in favor of induction chemotherapy was found regarding loco-regional recurrence, disease-free survival and overall survival. A subgroup analysis of individual data from cN2 patients showed statistically significant overall survival benefit in favor of induction chemotherapy. The included studies did not directly compare toxicity between the groups and no statistical analysis was performed regarding safety outcomes. CONCLUSIONS: Based on the available studies, induction chemotherapy when administered before surgery with curative intent did not improve clinical outcomes in locoregionally advanced oral cavity cancers patients. Clinically assessed N2 patients might benefit from induction chemotheraphy

INTRODUÇÃO: Os tumores da cavidade oral localmente avançados são neoplasias agressivas e com alto risco de recaída após o tratamento radical definitivo. O presente estudo foi realizado para avaliar a eficácia e segurança da quimioterapia de indução antes da cirurgia em pacientes com câncer de cavidade oral. MÉTODOS: Uma revisão sistemática da literatura foi realizada e apenas ensaios clínicos randomizados prospectivos fase III que comparavam a quimioterapia de indução seguida de cirurgia com ou sem radioterapia pósoperatória (Grupo QT) à cirurgia com ou sem radioterapia pós-operatória (Grupo Controle) foram elegíveis. Dois autores selecionaram os estudos de forma independente, respeitando os critérios de elegibilidade preestabelecidos. Avaliou-se também o risco de viés dos estudos incluídos. RESULTADOS: No total, dois estudos foram selecionados. Quatrocentos e cinquenta e um pacientes foram aleatoriamente randomizados para o Grupo QT (n = 226) e para o Grupo Controle (n = 225). A maioria dos pacientes tinha tumores em estádios clínicos III/IV (89,1%). Ambos os estudos foram classificados como tendo baixo risco de viés. Nenhum benefício estatisticamente significante em favor da quimioterapia de indução foi encontrado quanto à recorrência locorregional, à sobrevida livre de doença e à sobrevida global. A análise de subgrupo com dados individuais dos pacientes com doença cervical linfonodal N2 demonstrou benefício estatisticamente significante em sobrevida global no grupo que recebeu quimioterapia de indução. Nenhuma análise estatística foi realizada em relação à segurança das estratégias de tratamento, uma vez que os estudos incluídos não avaliaram diretamente esse desfecho. CONCLUSÕES: Com base nos estudos disponíveis, a quimioterapia de indução não melhora os resultados clínicos em pacientes com câncer de cavidade oral quando administrada antes da cirurgia radical com intenção curativa. O subgrupo de pacientes com doença linfonodal cervical N2 é aquele que eventualmente poderia se beneficiar da estratégia de quimioterapia de indução / INTRODUCTION: Locoregionally advanced oral cavity cancers are aggressive tumors with high risk of relapse after definitive treatment. This study was performed to assess the effectiveness and safety of induction chemotherapy prior to surgery for untreated oral cavity cancer patients. METHODS: Only prospective phase III randomized studies comparing induction chemotherapy followed by surgery with or without postoperative radiotherapy (Chemo Group) compared with surgery with or without postoperative radiotherapy (Control Group) were eligible. Two of the authors independently selected and assessed the studies regarding eligibility criteria and risk of bias. RESULTS: Two studies were selected. A total of 451 patients were randomly assigned to Chemo Group (n = 226) versus Control Group (n = 225). Most patients had tumors at clinical stages III/IV (89.1%). Both trials were classified as having low risk of bias. No significant overall benefit in favor of induction chemotherapy was found regarding loco-regional recurrence, disease-free survival and overall survival. A subgroup analysis of individual data from cN2 patients showed statistically significant overall survival benefit in favor of induction chemotherapy. The included studies did not directly compare toxicity between the groups and no statistical analysis was performed regarding safety outcomes. CONCLUSIONS: Based on the available studies, induction chemotherapy when administered before surgery with curative intent did not improve clinical outcomes in locoregionally advanced oral cavity cancers patients. Clinically assessed N2 patients might benefit from induction chemotheraphy