Johannes Lutterbach

Radiosurgery followed by planned observation in patients with one to three brain metastases.

OBJECTIVE To analyze the role of radiosurgery alone in patients with brain metastases. There were three specific study goals: 1) to determine whether survival of patients selected for this treatment approach can be predicted successfully by use of the recursive partitioning analysis classification defined by the Radiation Therapy Oncology Group; 2) to evaluate local control; and 3) to identify risk factors of cerebral failure. METHODS A total of 101 patients with Karnofsky Performance Scale scores of at least 50 and up to three brain metastases, each 3 cm or less in maximum diameter, were treated with radiosurgery alone. Survival, local control, distant brain freedom from progression (FFP), and overall brain FFP were evaluated according the method of Kaplan and Meier. Risk factors for survival and overall brain FFP were analyzed using the Cox model. RESULTS Median survival was 13.4 months, 9.3 months, and 1.5 months for patients in recursive partitioning analysis Classes 1, 2, and 3, respectively (P < 0.0001). At 1 year, local control, distant brain FFP, and overall brain FFP were 91, 53, and 51%, respectively. An interval greater than 2 years between diagnosis of the primary tumor and diagnosis of brain metastases and the presence of a single brain metastasis were associated with significantly higher overall brain FFP. CONCLUSION Recursive partitioning analysis classification successfully predicted survival. Radiosurgery alone yielded high local control. Overall brain FFP was highest in patients with an interval greater than 2 years between primary diagnosis and diagnosis of a single brain metastasis.

Malignant pineal parenchymal tumors in adult patients : Patterns of care and prognostic factors

OBJECTIVE The aim of our study was to analyze patterns of care and to identify prognostic factors in patients at least 18 years of age who received radiotherapy for malignant pineal parenchymal tumors. METHODS In a multicenter, retrospective study, we analyzed data for 37 previously published cases and 64 patients treated at the participating institutions. RESULTS A total of 56 patients received postoperative radiotherapy, and 45 patients received primary radiotherapy. Chemotherapy was administered to 34 patients. The median follow-up period was 38 months, and median overall survival was 100 months. The variables that significantly influenced overall survival were the extent of disease (localized versus disseminated;P = 0.0002), differentiation (pineal parenchymal tumor of intermediate differentiation versus pineoblastoma;P = 0.001), and residual disease (≥50% versus <50% reduction in size;P < 0.0001). In a multivariate analysis, the parameters turned out to be independent risk factors. The median survival in patients with local or spinal failure was 15 months. Local control was better in older patients (≥32 yr versus <32 yr;P = 0.02). Spinal control was more successful in patients with pineal parenchymal tumors of intermediate differentiation than it was in patients with pineoblastomas (P = 0.03). Nine of 45 treatment failures occurred later than 5 years after treatment. CONCLUSION Stage, histological characteristics, and response are independent risk factors in adults with malignant pineal parenchymal tumors. Late relapses are common.

Do religious or spiritual beliefs influence bereavement? A systematic review.

Background: Responses to bereavement may be influenced by characteristics such as age or gender, but also by factors like culture and religion. Aim: A systematic review was undertaken to assess whether spiritual or religious beliefs alter the process of grief and/or bereavement. Methods: Fifteen computerized databases were searched. Thirty-two studies met the inclusion criteria. Evidence was graded according to the standard grading system of the Clinical Outcomes Group and by the SIGNAL score. Results: In total, 5715 persons were examined: 69% women, 87% white, 83% protestant. Ninety-four percent of studies show some positive effects of religious/spiritual beliefs on bereavement, but there was a great heterogeneity regarding included populations and outcome measurements. Conclusion: Available data do not allow for a definite answer on whether religious/spiritual beliefs effectively influence bereavement as most studies suffer from weaknesses in design and methodological flaws. Further research is needed. Recommendations for further research are given. Palliative Medicine 2007; 21: 207—217

MULTIVARIATE ANALYSIS OF PROGNOSTIC FACTORS IN PATIENTS WITH GLIOBLASTOMA

Background: To identify prognostic factors for overall survival in patients with newly diagnosed glioblastoma undergoing radiation therapy. Patients and Methods: From January 1980 to June 2000, we treated 432 consecutive patients with glioblastoma at out institution. 17 patients were excluded from the analysis for various reasons. Mean age of the 415 patients who were included in the study was 59 years (19–81 years), Karnofsky performance status (KPS) was ≥ 70 in 280 patients. 343 patients underwent resection, 72 had a biopsy. Various fractionation schemes were used (conventional fractionation, n = 112; hypofractionation, n = 94; accelerated hyperfractionation, n = 209). Survival probabilities were estimated using the method of Kaplan and Meier. Multivariate analysis was done with a Cox regression model. Results: By July 2001, 406 patients had died. Medial overall survival was 8.2 months. Of ten factors considered in a proportional hazards model stratified for treatment (fractionation scheme and type of surgery), significant variables in a multivariate model were age (50–64 years vs < 50 years [RR 1.35; 95% CI 1.02–1.78], ≥ 65 years vs < 50 years [RR 2.08; 95% CI 1.54–2.81]), performance status (KPS < 70 vs ≥ 70 [RR 1.53; 95% CI 1.23–1.90]), and central tumor location (yes vs no [RR 1.39; 95% CI 1.04–1.87]). Blood hemoglobin (Hb) values were available in 318 patients and serum lactate dehydrogenase (LDH) levels in 234 patients. 89 patients were anemic (Hb men < 13 g/dl, women < 12 g/dl), in 80 patients the LDH level was raised beyond the upper limit of the normal range (> 240 U/l). By including the three significant variables, both parameters had an additional significant effect with an estimated relative risk of about 1.4 in their corresponding subgroups. Conclusion: Besides established prognostic factors, anemia and raised serum LDH levels may negatively influence outcome in glioblastoma patients. Our results from data-dependent modeling have to be confirmed by independent studies.Hintergrund: Die vorliegende Studie untersucht Prognosefaktoren für das Gesamtüberleben bei Patienten, die aufgrund eines neu diagnostizierten Glioblastoms bestrahlt wurden. Patienten und Methodik: Von Januar 1980 bis Juni 2000 wurden 432 Glioblastompatienten an unserer Klinik behandelt. 415 Patienten wurden in die Analyse einbezogen. Das durchschnittliche Alter betrug 59 Jahre (19–81 Jahre), der Karnofsky-Performance-Status (KPS) war bei 280 Patienten ≥ 70. Bei 343 Patienten wurde der Tumor reseziert, bei 72 Patienten biopsiert. Die Strahlentherapie erfolgte konventionell fraktioniert (n = 112), hypofraktioniert (n = 94) oder akzeleriert hyperfraktioniert (n = 209). Die Schätzung der Überlebenswahrscheinlichkeiten erfolgte mit der Methode von Kaplan und Meier. Multivariate Analysen wurden mit einem Regressionsmodell nach Cox durchgeführt. Ergebnisse: Bis Juli 2001 waren 406 Patienten verstorben. Das mediane Gesamtüberleben betrug 8,2 Monate. Von zehn Faktoren, die in einem nach Resektionsstatus und Fraktionierungsschema stratifizierten Proportional-Hazards-Modell untersucht wurden, erwiesen sich als signifikant: Alter (50–64 Jahre vs. < 50 Jahre) [RR 1,35; 95%-CI 1,02–1,78], ≥ 65 Jahre vs. < 50 Jahre [RR 2,08; 95%-CI 1,54–2,81]), Allgemeinzustand (KPS < 70 vs. ≥ 70 [RR 1,53; 95%-CI 1,23–1,90]) und zentraler Tumorsitz (ja vs. nein [RR 1,39; 95%-CI 1,04–1,87]). Werte für Hämoglobin (Hb) und Serum-Lactat-Dehydrogenase (LDH) lagen bei 318 bzw. 234 Patienten vor. 89 Patienten waren anämisch (Hb Männer < 13 g/dl, Frauen < 12 g/dl), bei 80 Patienten war der LDH-Wert erhöht (> 240 U/l). Unter Berücksichtigung der drei signifikanten Variablen übten beide Parameter in den jeweiligen Untergruppen einen zusätzlichen Effekt aus mit einem relativen Risiko von etwa 1,4. Schlussfolgerung: Neben bekannten Prognosefaktoren beeinflussen erniedrigte Hb- und erhöhte LDH-Werte das Überleben bei Patienten mit Glioblastom negativ.

Gliosarcoma: a clinical study

BACKGROUND AND PURPOSE Gliosarcomas are rare biphasic neoplasms of the central nervous system composed of a glioblastoma multiforme (GBM) admixed with a sarcomatous component. There are conflicting reports regarding their clinical aggressiveness. Four hundred and twenty-two consecutive patients with GBM were treated at our hospital between 1980 and 1999, among them 12 gliosarcomas. The goal of this study was to examine clinical features, treatment, survival and patterns of failure of gliosarcoma patients and to compare them with the entire group of GBM patients. This comparison was refined by a matched pair analysis with a group of 12 GBM patients selected for age, Karnofsky performance status, resection status, fractionation scheme and total dose (control GBM group). MATERIALS AND METHODS Seven gliosarcoma patients were male, five female, with a median age of 56 years (range 37-76 years). The median tumor size was 4.5 cm (range 3-8 cm). The locations, all supratentorial, included temporal in six, parietal in five, frontal in four and occipital in one patient. All patients underwent tumor resection followed by postoperative radiation therapy. RESULTS Median survival was 11.5 months for the gliosarcoma group, 8.1 months for the entire GBM group (log rank test, P=0.16) and 11.0 months for the control GBM group (log rank test, P=0.36). All gliosarcoma patients had local tumor recurrences and died due to neurologic causes within 19.3 months after radiation therapy. CONCLUSIONS With regard to clinical features, survival and patterns of failure, gliosarcomas and GBM cannot be distinguished clinically. Therefore, the same principles should be applied for the treatment of these tumors.

Atypical teratoid/rhabdoid tumors in adult patients: case report and review of the literature.

Atypical teratoid/rhabdoid tumors (AT/RT) of the central nervous system are rare and extremely aggressive malignancies of early childhood. We report a case of AT/RT in an adult patient.A 30-year-old woman presented with headache, vomiting and ataxia during the second trimester of pregnancy. Magnetic resonance imaging revealed a posterior fossa mass. A gross total resection was performed. Pathological examination revealed an AT/RT. Despite the dismal prognosis the patient decided not to undergo an abortion. For this reason postoperative accelerated hyperfractionated radiotherapy was limited to the tumor region. Six months later the woman delivered a healthy baby. One week postpartum, a central nervous system recurrence localized apart from the primary lesion was treated with radiosurgery. Two months later a diffuse progression was noted. Despite a 6 week course of oral temozolomide, the tumor progressed and the patient died 11 months after diagnosis.Although survival was short, surgery and involved field radiotherapy yielded a progression-free interval of 9 months. This allowed the patient to carry pregnancy to term. Radiosurgery resulted in a complete remission of the first recurrence. Oral chemotherapy was not effective in controlling diffuse tumor spread.

Patients with brain metastases: hope for recursive partitioning analysis (RPA) class 3

PURPOSE The objectives of the present study were (a) to validate the prognostic classification derived from recursive partitioning analysis (RPA) of the Radiation Therapy Oncology Group (RTOG); (b) to identify prognostic factors in class 3; (c) to examine the impact of treatment related variables on the prognosis in class 3. PATIENTS AND METHODS Nine hundred and sixteen patients with brain metastases had resection and whole brain radiotherapy (WBRT, n = 257) or WBRT alone (n = 659) at our institution from 1985 to 2000. Patients were grouped into RPA classes 1, 2, and 3 (n = 67, 441, and 408, respectively). RESULTS Median survival of the whole group was 3.4 months. Median survival in classes 1, 2, and 3 was 8.2, 4.9, and 1.8 months, respectively. In class 3, age (<65 years vs. > or =65 years, relative risk (RR) 0.75), status of the primary tumor (controlled vs. uncontrolled, RR 0.86), and the number of brain metastases (single vs. multiple, RR 0.76) were independent prognostic variables. We defined three prognostic subgroups: class 3a (n = 51): age <65 years, controlled primary tumor, single brain metastasis; class 3c (n = 44): age > or =65 years, uncontrolled primary tumor, multiple brain metastases; class 3b (n = 313): all other patients. Median survival in classes 3a, 3b, and 3c was 3.2, 1.9, and 1.2 months, respectively (P < 0.0001). Intra-class comparisons showed that resection followed by WBRT yielded significantly better survival compared with WBRT alone. CONCLUSION Our results validate the RTOG RPA classification for patients with brain metastases. The variables age, status of the primary, and number of brain metastases allow the division of class 3 into prognostic subgroups. Even class 3 patients may benefit from more aggressive treatment strategies.

Fractionated stereotactic radiotherapy boost after post-operative radiotherapy in patients with high-grade gliomas

PURPOSE To determine the value and the toxicity of an additional fractionated stereotactic boost as used in the joint randomized EORTC-22972/MRC-BR10 study in patients with malignant gliomas. MATERIALS AND METHODS Seventeen patients (11 male, six female) with a high-grade glioma (two WHO III, 15 WHO IV) < or =4 cm in maximum diameter, with a good performance status (WHO > or =2), were treated with a fractionated stereotactic radiotherapy (SRT) boost to 20 Gy in four fractions following partial brain irradiation to a dose of 60 Gy in 30 fractions. This patient group was compared with historical data in a matched-pair analysis. RESULTS All patients were treated by conventional radiotherapy and a SRT boost (15 patients received 20 Gy and two patients 10 Gy). Acute side effects included fatigue (two), impairment of short-term memory (one) and worsening of pre-existing symptoms (one). No patient developed steroid dependence after SRT. One patient was re-operated for radiation necrosis. At a median follow-up of 25 months (9-50 months) 14 patients recurred locally. Survival was 77% at 1 year and 42% at 2 years; progression-free survival was 70% at 1 year and 35% at 2 years for all patients, respectively. Median survival for the whole patient group is 20 months. Comparison with a matched historical group showed a significantly better survival for the group treated with a stereotactic boost (P<0.0001). CONCLUSION A fractionated stereotactic boost after standard external beam radiotherapy in selected patients with high-grade glioma is feasible and well tolerated with low toxicity. Compared to historical data survival is significantly better with an additional SRT boost. However, its effectiveness has to be proven in a randomized trial.

The Brain Tumor Board: Lessons to Be Learned from an Interdisciplinary Conference

Background: The aim of this study is to analyze the work of the interdisciplinary Brain Tumor Board (BTB) which was established at Freiburg University Hospital in 1998. Patients and Methods: From January 1998 to December 2003, a total of 1,516 patients were discussed in 259 meetings of the BTB. The protocols of the BTB were analyzed retrospectively. Results: In 79% of the patients, the diagnosis was based on histological findings or a typical radiological appearance of a lesion, or both. This group was composed of 4 subgroups: 28% benign skull base tumors (19% meningiomas, 4% pituitary adenomas, 3% acoustic schwannomas, 2% others), 24% primary brain tumors of glial origin (8% glioblastomas, 12% gliomas other than glioblastomas, 5% oligoastrocytomas or oligodendrogliomas), 19% brain metastases, and 8% other brain or skull base tumors. In 13% of the cases, the exact diagnosis was still unknown when the patient was presented. 8% of the presentations were motivated by nontumorous interdisciplinary problems (e.g. arterio-venous malformations). The recommendations given by the BTB included: 23% further diagnostic procedures (11% non-invasive examinations, 12% stereotactic biopsies), 57% active antitumoral therapy (22% resection, 17% fractionated radiotherapy, 13% radiosurgery, 5% chemotherapy, <1% embolization), 20% no treatment (14% watchful waiting, 6% supportive care). 91% of the BTB recommendations were realized within 3 months. Conclusion: Interdisciplinary care seems to be particularly necessary in patients with benign skull base tumors, gliomas and brain metastases. Decisions made in a small interdisciplinary group of experts have a high potential of subsequently being realized.

Brain metastases in patients with cancer of unknown primary.

Between January 1985 and December 2000, 916 patients with brain metastases were treated with whole brain radiation therapy (WBRT) at the Department of Radiotherapy, University Hospital Freiburg. In 47 patients, a primary tumor could not be identified (cancer of unknown primary (CUP)). Sixteen patients had a solitary brain metastasis, 31 patients presented with multiple brain metastases. Surgical resection was performed in 15 patients, biopsy alone in 12 patients. WBRT was applied with daily fractions of 2 or 3Gy to a total dose of 50 or 30Gy, respectively. According to the recursive partitioning analysis (RPA) classes of the Radiation Therapy Oncology Group for patients with brain metastases none of the patients met the criteria for Class I, 23 for Class II, and 24 for Class III.The median overall survival (OS) for all patients with brain metastases (n = 916) was 3.4 and 4.8 months for patients with CUP (p = 0.45). In patients with CUP (n = 47) the median OS for patients with a single brain metastasis was 7.3 versus 3.9 months for patients with multiple brain metastases (p = 0.05). Median OS for patients with a Karnofsky performance status (KPS) ≥70 was 6.3 months versus 3.2 months for KPS <70 (p = 0.01).At multivariate analysis performance status and resection status could be identified as independent prognostic factors for the OS.