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No description available.

One of the main objectives of combining radiation treatment and chemotherapy is to obtain a therapeutic gain by an improved tumour control with less or no enhancement of normal tissue toxicity. The optimal schedule for the combined treatment of cisplatin-radiation is still under investigation. Neither the optimal time interval, nor the most adequate sequence of administration of cisplatin and radiation are known. The results of the trials are also inconclusive. Some trials showed a supra-additive effect from the administration of cisplatin before radiotherapy, others, on contrary, from the injection of drug after radiotherapy. The present work encompasses the major challenges brought by the combined modality treatment: cisplatin-radiotherapy. The major goal of this work was to investigate the optimal treatment sequencing between cisplatin and radiotherapy and also the optimal schedule for head and neck carcinomas. Therefore, a computer-based tumour model with literature-given biological parameters has been developed which has allowed the simulation of treatment with radiation and chemotherapy. Radiotherapy has been simulated on the virtual tumour and the effects of radiotherapy on tumour regression and regrowth have been analyzed. Also, the mechanisms of cisplatin's action on tumour have been implemented, and the phenomena of drug resistance and tumour repopulation during chemotherapy studied. Finally, the combined modality treatment has been simulated, and the effect of drug-radiation interaction on tumour behaviour evaluated. The current investigation has shown that cisplatin administered immediately before radiation gives similar tumour control to the post-radiation sequencing of the drug. Furthermore, the killing effect of the combined modality treatment on tumour increases with the increase in cell recruitment. The individual cell kill produced by cisplatin and radiation leads to an additive-only tumour response when the treatments are given concurrently, and for a synergistic effect cisplatin must potentiate the effect of radiation. The final conclusion, by which cisplatin administered on a daily basis leads to a better tumour control than cisplatin administered weekly, is in accordance with the latest trial results on head and neck cancers. Therefore, treatment regimens that correlate better with the pharmacokinetics and the radiobiological properties of the therapeutic agents result in better outcomes. / Thesis (Ph.D.)--School of Chemistry and Physics, 2004.

Brain metastases are treated with surgery, radiotherapy, radiosurgery, and chemotherapy. In this review, recently published studies concerning different treatment strategies are presented with respect to solitary lesions, multiple metastases, and recurrent tumor growth. Selection criteria for the appropriate therapy are: control of the primary tumor, extent of extracerebral metastases, time interval between diagnosis of the primary tumor and the development of cerebral lesions, number of cerebral metastases, Karnofsky performance scale score, and age. Treatment approaches were evaluated with respect to median survival time and quality of life. A singular brain metastasis can be treated with surgery or with radiosurgery. Especially when the primary tumor is under control, there are few extracerebral lesions which are stable, the Karnofsky performance scale score is above 70, the lesion is larger than 3 cm in diameter and surgically accessible surgery is the treatment of choice. Postoperative adjuvant radiotherapy may delay relapse. Median survival time ranges between 10 to 18 months. Radiosurgery can be applied in lesions smaller than 3 cm in diameter and is the treatment of choice in lesions which are surgically not accessible. Multiple metastases are treated either by conventional radiotherapy, radiosurgery or surgery. Commonly, no more than 3 lesions are approached by either surgery or radiosurgery. Median survival time ranges between 6 to 9 months for both treatment concepts, but without therapy only is 4–6 weeks. According to the clinical and neurological condition of the patient, recurrent brain metastases can be treated by operation, reirradiation, or radiosurgery. The efficacy of chemotherapy depends on the chemosensitivity of the primary tumor and the ability to penetrate the blood-brain barrier. Long-term survivors with cancer disease encourage to perform active treatment strategies. / Hirnmetastasen werden durch Operation, Ganzhirnbestrahlung, Radiochirurgie und Chemotherapie behandelt. In dieser Übersichtsarbeit werden kürzlich publizierte Studien bezüglich der Therapiekonzepte für solitäre Läsionen, multiple Metastasen und Tumorrezidive vorgestellt. Auswahlkriterien für eine angemessene Behandlung sind: Kontrolle des Primärtumors, Ausmaß der extrakraniellen Metastasen, Zeitintervall zwischen Diagnose des Primärtumors und dem Auftreten der Hirntumoren, Anzahl der zerebralen Metastasen, Karnofsky-Performance-Scale-Score und Lebensalter. Behandlungskonzepte wurden nach der medianen Überlebenszeit und Lebensqualität ausgewertet. Singuläre Hirnmetastasen können operativ oder radiochirurgisch behandelt werden. Insbesondere wenn der Primärtumor unter Kontrolle ist, wenige extrazerebrale Läsionen bestehen und diese stabil sind, der Karnofsky-Performance-Scale-Score über 70 ist, die Tumoren größer als 3 cm im Durchmesser und chirurgisch erreichbar sind, ist die Operation die Methode der Wahl. Postoperative adjuvante Strahlentherapie kann erneute Progression verzögern. Die mediane Überlebenszeit liegt zwischen 10 und 18 Monaten. Für Läsionen, die kleiner als 3 cm sind und chirurgisch nicht erreicht werden können, ist die Radiochirurgie die Therapie der Wahl. Multiple Metastasen können durch konventionelle Ganzhirnbestrahlung, Radiochirurgie oder Operation behandelt werden. Im allgemeinen werden nicht mehr als 3 Herde operativ oder radiochirurgisch angegangen. Die mediane Überlebenszeit liegt bei beiden Therapieformen zwischen 6 und 9 Monaten, ohne Behandlung hingegen bei nur 4–6 Wochen. Entsprechend dem klinischen und neurologischen Zustand der Patienten können Rezidive von Hirnmetastasen durch chirurgische Entfernung, erneute Bestrahlung oder durch Radiochirurgie therapiert werden. Die Wirkung der Chemotherapie hängt von der Chemosensitivität des Primärtumors und der Durchlässigkeit der Blut-Hirn-Schranke für das Chemotherapeutikum ab. Langzeitüberleber motivieren zu aktiven Behandlungsstrategien. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

Medulloblastoma (MB) is a malignant embryonal tumor of the posterior fossa belonging to the family of primitive neuro-ectodermic tumors (PNET). MB generally occurs in pediatric age, but in 14–30% of cases, it affects the adults, mostly below the age of 40, with an incidence of 0.6 per million per year, representing about 0.4–1% of tumors of the nervous system in adults. Unlike pediatric MB, robust prospective trials are scarce for the post-puberal population, due to the low incidence of MB in adolescent and young adults. Thus, current MB treatments for older patients are largely extrapolated from the pediatric experience, but the transferability and applicability of these paradigms to adults remain an open question. Adult MB is distinct from MB in children from a molecular and clinical perspective. Here, we review the management of adult MB, reporting the recent published literature focusing on the effectiveness of upfront chemotherapy, the development of targeted therapies, and the potential role of a reduced dose of radiotherapy in treating this disease.