The Role of Stereotactic Radiosurgery in the Management of Foramen Magnum Meningiomas-A Multicenter Analysis and Review of the Literature.

BACKGROUND: Foramen magnum meningiomas (FMMs) represent a considerable neurosurgical challenge given their location and potential morbidity. Stereotactic radiosurgery (SRS) is an established non-invasive treatment modality for various benign and malignant brain tumors. However, reports on single-session or multisession SRS for the management and treatment of FMMs are exceedingly rare. We report the largest FMM SRS series to date and describe our multicenter treatment experience utilizing robotic radiosurgery. METHODS: Patients who underwent SRS between 2005 and 2020 as a treatment for a FMM at six different centers were eligible for analysis. RESULTS: Sixty-two patients met the inclusion criteria. The median follow-up was 28.9 months. The median prescription dose and isodose line were 14 Gy and 70%, respectively. Single-session SRS accounted for 81% of treatments. The remaining patients received three to five fractions, with doses ranging from 19.5 to 25 Gy. Ten (16%) patients were treated for a tumor recurrence after surgery, and thirteen (21%) underwent adjuvant treatment. The remaining 39 FMMs (63%) received SRS as their primary treatment. For patients with an upfront surgical resection, histopathological examination revealed 22 World Health Organization grade I tumors and one grade II FMM. The median tumor volume was 2.6 cubic centimeters. No local failures were observed throughout the available follow-up, including patients with a follow-up ≥ five years (16 patients), leading to an overall local control of 100%. Tumor volume significantly decreased after treatment, with a median volume reduction of 21% at the last available follow-up (p < 0.01). The one-, three-, and five-year progression-free survival were 100%, 96.6%, and 93.0%, respectively. Most patients showed stable (47%) or improved (21%) neurological deficits at the last follow-up. No high-grade adverse events were observed. CONCLUSIONS: SRS is an effective and safe treatment modality for FMMs. Despite the paucity of available data and previous reports, SRS should be considered for selected patients, especially those with subtotal tumor resections, recurrences, and patients not suitable for surgery.

Correction to: Retrospective analysis of fractionated intensity-modulated radiotherapy (IMRT) in the interdisciplinary management of primary optic nerve sheath meningiomas.

An amendment to this paper has been published and can be accessed via the original article.

Retrospective analysis of fractionated intensity-modulated radiotherapy (IMRT) in the interdisciplinary management of primary optic nerve sheath meningiomas.

BACKGROUND: As optic nerve sheath meningiomas (ONSM) are rare, there are no prospective studies. Our retrospective analysis focusses on a cohort of patients with uniform disease characteristics all treated with the same radiotherapy regimen. We describe treatment decision making, radiotherapy planning and detailed neuro-ophthalmological outcome of the patients. METHODS: 26 patients with unilateral ONSM extending only to the orbit and the optic canal were evaluated for neuro-ophthalmological outcome. Radiation treatment was planned in a simultaneous integrated boost approach to gross tumor volume (GTV) + 2 mm / 5 mm to 54 Gy / 51 Gy in 1.8 Gy / 1.7 Gy fractions. Follow-up was done by specialized neuro-ophthalmologists. Visual acuity and visual field defects were evaluated after therapy as well as during follow-up. RESULTS: Interdisciplinary treatment decision for patients with ONSM follows a rather complex decision tree. Radiation treatment planning (equivalent uniform dose (EUD), maximum dose to the optic nerve) improved with experience over time. With this patient selection visual acuity as well as visual field improved significantly at first follow-up after treatment. For visual acuity this also applied to patients with severe defects before treatment. Long term evaluation showed 16 patients with improved visual function, 6 were stable, in 4 patients visual function declined. Interdisciplinary case discussion rated the visual decline as radiation-associated in two patients. CONCLUSIONS: With stringent patient selection radiotherapy for unilateral primary ONSM to 51 Gy / 54 Gy is safe and leads to significantly improved visual function. Interdisciplinary treatment decision and experience of the radiation oncology team play a major role.

Specific toxicity after stereotactic body radiation therapy to the central chest : A comprehensive review.

The toxicity of stereotactic body radiation therapy in the central chest remains an unsettled issue. The collected data concerning the observed complications are poorly understood and are limited in their quantity and quality, thus hampering a precise delineation of treatment-specific toxicity. The majority of complications scored as toxicity grade 5, namely respiratory failure and fatal hemoptysis, are most likely related to multiple competing risks and occurred at different dose fractionation schemas, e. g., 10-12 fractions of 4-5 Gy, 5 fractions of 10 Gy, 3 fractions of 20-22 Gy, and 1 fraction of 15-30 Gy. Further investigations with longer follow-up and more details of patients' pretreatment and tumor characteristics are required. Furthermore, satisfactory documentation of complications and details of dosimetric parameters, as well as limitation of the wide range of possible fractionation schemes is also warranted for a better understanding of the risk factors relevant for macroscopic damage to the serially organized anatomic structure within the central chest.

Sodium phosphaethynolate as a building block for heterocycles.

Phosphorus-containing heterocycles have evolved from laboratory curiosities to functional components, such as ligands in catalytically active metal complexes or molecular constituents in electronic devices. The straightforward synthesis of functionalized heterocycles on a larger scale remains a challenge. Herein, we report the use of the phosphaethynolate (OCP)(-) anion as a building block for various sterically unprotected and functionalized hydroxy substituted phosphorus heterocycles. Because the resulting heterocycles are themselves anions, they are building blocks in their own right and allow further facile functionalization. This property may be of interest in coordination chemistry and material science.

Fractionated stereotactic radiotherapy in patients with optic nerve sheath meningioma.

PURPOSE: To evaluate the effectiveness of fractionated stereotactic radiotherapy (SFRT) in the treatment of optic nerve sheath meningioma (ONSM). METHODS AND MATERIALS: Between 1993 and 2005, 109 patients (113 eyes) with primary (n = 37) or secondary (n = 76) ONSM were treated according to a prospective protocol with SFRT to a median dose of 54 Gy. All patients underwent radiographic, ophthalmologic, and endocrine analysis before and after SFRT. Radiographic response, visual control, and late side effects were endpoints of the analysis. RESULTS: Median time to last clinical, radiographic, and ophthalmologic follow up was 30.2 months (n = 113), 42.7 months (n = 108), and 53.7 months (n = 91), respectively. Regression of the tumor was observed in 5 eyes and progression in 4 eyes, whereas 104 remained stable. Visual acuity improved in 12, deteriorated in 11, and remained stable in 68 eyes. Mean visual field defects reduced from 33.6% (n = 90) to 17.8% (n = 56) in ipsilateral and from 10% (n = 94) to 6.7% (n = 62) in contralateral eyes. Ocular motility improved in 23, remained stable in 65, and deteriorated in 3 eyes. Radiographic tumor control was 100% at 3 years and 98% at 5 years. Visual acuity was preserved in 94.8% after 3 years and in 90.9% after 5 years. Endocrine function was normal in 90.8% after 3 years and in 81.3% after 5 years. CONCLUSIONS: SFRT represents a highly effective treatment for ONSM. Interdisciplinary counseling of the patients is recommended. Because of the high rate of preservation of visual acuity we consider SFRT the standard approach for the treatment of ONSM. Prolonged observation is warranted to more accurately assess late visual impairment. Moderate de-escalation of the radiation dose might improve the preservation of visual acuity and pituitary gland function.

First results of the federal quality assurance group ("Arztliche Stelle") in radiotherapy in Baden-Württemberg: part 2.

PURPOSE: Part 2 of this study presents the results of the clinical audits of the "Arztliche Stelle" (AS) concerning process quality in the radiation therapy units in Baden-Württemberg, Germany. MATERIAL AND METHODS: The process quality of nine main test groups (laws, organizations, technical equipment, GMP [Good Medical Practice] principles, radiotherapy, radiation procedure, follow-up, discharge report, physics) were questioned by the AS commission and evaluated in a four-stage classification (1-4; none to grave deficiencies). RESULTS: In 18 institutes (81%), the medical and physical-technical inspection, including radiation protection for patients and staff, revealed very high to high quality, safe treatment commensurate with current standards was guaranteed once the suggestions for improvement given by the experts had been implemented. In four institutes (18%), the inspection showed a still satisfactory quality but a shorter period for reinspection was recommended. The most frequent comments/deficiencies were found in staff structures (32%), in continuous education/training for staff (32%), in informed patient consent (41%), follow-up (45%), and/or a unclearly formulated discharge report for the referring physicians (45%). CONCLUSION: The medical and physical-technical examination of radiation treatment in the vast majority (81%) of the radiation therapy institutes in Baden-Württemberg showed a very high or high quality. Most of the comments and deficiencies concerned the sector of systematic continued training for staff, giving clear explanations to patients, structured follow-up, and the state of the medical discharge reports. These deficiencies, however, do not represent any immediate danger to the patient through any deficiencies in therapy. The experience gained by the AS could act as a model for quality improvement and could also be transmitted to other medical sectors to retain quality standards. The various specialist associations are called upon to gradually adopt the suggestions for quality improvements which are based on concrete as-is analyses by steadily aligning practice with theory. This would enable the steadily rising demands of quality assurance to be sustainably implemented through practicable models.

[First results of the federal quality assurance group ("Arztliche Stelle") in radiotherapy in baden-württemberg: part 1]. / Erste Ergebnisse der Qualitätssicherung durch Arztliche Stellen in der Radiotherapie am Beispiel Baden-Württemberg: Teil 1.

PURPOSE: To evaluate the structure quality (medical staff, linear accelerators, and patients) of radiotherapy units based on the clinical audits by the "Arztliche Stelle" (this institution is based on federal German law) in Baden-Württemberg. MATERIAL AND METHODS: External audits (performed by at least two radiation oncologists, one radiation physicist, and a member of the administration) of recently completed charts by designated reviewers using appropriate checklists developed by the federal task group ("Arztliche Stelle") were used. RESULTS: In the interval from 2005 to 2007, 60 linear accelerators in 24 radiotherapy units served a population of approximately 10.7 million inhabitants (178,000 inhabitants/linear accelerator). 28,210 people with malignant tumors were treated in these units in 2007. These patients were served by 127 radiation oncologists, 83 radiation physicists, and 235 technologists. The ratio of patients irradiated annually to staff would become 222 (range 85-400) for a radiation oncologist, 339 for a radiation physicist (range 170-538), and 120 for a technologist (range 48-189). In five of seven departments (71%), new staff was employed following the recommendations of the auditors. CONCLUSION: Clinical audits by the "Arztliche Stelle" are highly effective to evaluate the structure quality of radiotherapy units. Based on these audits realistic data for staff requirements were gained. Making use of these data, guidelines for average minimum personnel necessary for good patient care were calculated. Personnel requirements may vary related to specific needs (teaching, research) of the treatment program and should be accounted for when discussing with the administration. The recommendations of the auditors of the "Arztliche Stelle" resulted in the new employment of additional staff.

Moderate risk-adapted dose escalation with three-dimensional conformal radiotherapy of localized prostate cancer from 70 to 74 Gy. First report on 5-year morbidity and biochemical control from a prospective Austrian-German multicenter phase II trial.

PURPOSE: Evaluation of late side effects and biochemical control (bNED) 5 years after three-dimensional radiotherapy with moderate, risk-adapted dose escalation. PATIENTS AND METHODS: From 03/1999 to 07/2002, 486 patients have been registered in the prospective Austrian-German multicenter phase II trial (AUGE). 399 (82%) localized prostate cancer patients (T1-3 Nx/N0 M0) were evaluated. The low- and intermediate-risk groups were treated with 70 Gy, the high-risk group with 74 Gy, respectively. Additional hormonal therapy (HT) was recommended for intermediate- and high-risk group patients. Late toxicity (EORTC/RTOG) and bNED (ASTRO and Phoenix) were prospectively assessed. RESULTS: Median follow-up was 65 months. Distribution concerning risk groups (low-, intermediate-, high-risk group) showed 29%, 50% and 21% of patients, respectively. HT was given in 87% of patients. The 5-year actuarial rates of late side effects grade > or = 2 for 70 Gy/74 Gy were 28%/30% (gastrointestinal; p = 0.73) and 19%/34% (urogenital; p = 0,06). The 5-year actuarial bNED rate stratified by risk groups (low-, intermediate-, high-risk group) was 74%, 66% and 50% (ASTRO), and 81%, 80% and 60% (Phoenix), respectively. Within multivariate analysis T-stage and initial prostate specific antigen were significant factors influencing bNED (ASTRO) whereas Gleason Score and duration of HT were not. CONCLUSION: Dose escalation within standard three-dimensional conformal radiotherapy (3D-CRT) up to a level of 74 Gy did not result in significantly increased gastrointestinal side effects, whereas urogenital side effects showed an increase close to significance. However, the total number of patients with severe toxicity was low. To achieve high tumor control rates with acceptable treatment-related morbidity, local doses of at least 74 Gy should be considered, in particular for intermediate- or high-risk patients applying 3D-CRT.

Randomized study of postoperative radiotherapy and simultaneous temozolomide without adjuvant chemotherapy for glioblastoma.

PURPOSE: To evaluate the efficacy of simultaneous postoperative temozolomide radiochemotherapy in glioblastoma patients. PATIENTS AND METHODS: From February 2002 to July 2004, n = 65 patients from 11 German centers with macroscopic complete tumor resection were randomized to receive either postoperative radiotherapy alone (RT, n = 35) or postoperative radiotherapy with simultaneous temozolomide (RT + TMZ, n = 30). Patients were stratified according to age (< or =/>50 years) and WHO performance score (0-1 vs. 2). RT consisted of 60 Gy in 30 fractions. In the RT + TMZ arm, oral TMZ was administered daily at a dose of 75 mg/m(2) including weekends (40-42 doses). Adjuvant treatment was not given, but in both arms, patients with recurrent tumors and in good condition (WHO 0-2) were scheduled for salvage chemotherapy with TMZ. RESULTS: The trial was stopped early due to the results of EORTC-study 26981-22981 that showed a survival benefit for the combination of concomitant and adjuvant TMZ compared to radiotherapy alone. In total, 62/65 patients were evaluable. Stratification variables were well balanced (< or = 50 years 26% vs. 20%, WHO 0-1 91% vs. 100%). Neither overall survival (median 17 vs. 15 months) nor progression-free survival (median 7 vs. 6 months) differed significantly between the two arms. In the RT (RT + TMZ) arm, 76% (62%) of the progressing patients received salvage chemotherapy with TMZ, 36% (50%) had a second resection. There was a time-constant trend for increased general quality of life (EORTC questionnaire QLQ C30) and brain-specific quality of life (EORTC questionnaire B20) in the combined arm. Lymphopenia G3-4 was more frequent (33 vs. 6%) in the RT + TMZ arm. CONCLUSION: After early closure of this trial, a benefit for progression-free survival for simultaneous TMZ radiochemotherapy alone could not be demonstrated. In both arms, salvage therapies were frequently used and probably had a major effect on overall survival.

Proctitis after external-beam radiotherapy for prostate cancer classified by Vienna Rectoscopy Score and correlated with EORTC/RTOG score for late rectal toxicity: results of a prospective multicenter study of 166 patients.

PURPOSE: To evaluate the Vienna Rectoscopy Score (VRS) as a feasible and effective tool for detecting and classifying pathologic changes in the rectal mucosa after radiotherapy (RT) for prostate cancer, and, also, to correlate its findings with the European Organization for Research and Treatment of Cancer (EORTC)/Radiation Therapy Oncology Group (RTOG) score for late rectal toxicity. METHODS AND MATERIALS: A total of 486 patients with localized prostate cancer underwent external-beam RT up to 70 or 74 Gy within an Austrian-German prospective multicenter trial. In 166 patients, voluntary rectal sigmoidoscopy was performed before and at 12 and/or 24 months after RT. Pathologic findings such as telangiectasia, congested mucosa, and ulcers were graded (Grades 0-3) and summarized according to the VRS. Late rectal side effects (EORTC/RTOG) were documented and correlated with the corresponding VRS. RESULTS: Before RT, 99% had a VRS score of 0. The median follow-up was 40 months. Overall, a late rectal side effects grade or score 1-3 was detected in 43% by EORTC/RTOG compared with 68% by VRS (p < 0.05). Grades 0, 1, 2, and 3 late rectal side effects were found using EORTC/RTOG in 57%, 11%, 28%, and 3%, respectively; the corresponding percentages were 32%, 22%, 32%, and 14% for a VRS of 0, 1, 2, and 3, respectively. A significant coherence between the VRS and EORTC/RTOG was found (p < 0.01). CONCLUSIONS: The VRS is a feasible and effective tool for describing and classifying pathologic findings in the rectal mucosa after RT within a multicenter trial. The VRS and EORTC/RTOG showed a high coherence. However the VRS was significantly more sensitive.

Radiotherapy in the management of Kaposi's sarcoma.

INTRODUCTION: Of all types of Kaposi's sarcoma (KS), only AIDS (acquired immunodeficiency syndrome)-related KS is of clinical importance, although its incidence has significantly declined in the last years. KS is considered a radiosensitive tumor, and good palliation of symptoms can be achieved with radiotherapy. MATERIAL AND METHODS: Evident radiotherapy data in the available literature were reviewed to analyze and evaluate indications, techniques, dose concepts and outcomes in radiation treatment of KS. RESULTS: Good palliation of KS symptoms can be achieved by radiotherapy, with more than 90% response and 70% complete remission. For patients with far advanced AIDS, a single dose of 8 Gy is preferable. The following doses have been shown to be sufficient: 15 Gy for oral lesions, 20 Gy for lesions involving the eyelids, conjunctivae and genitals, 30-40 Gy in single doses of 2 Gy for cutaneous lesions. Side effects are rare, and radiation is usually well tolerated, with minimal skin reactions -- except for patients with mucosa lesions, where a high degree of mucositis is often observed. CONCLUSION: Radiotherapy has its place in the management of KS as an efficient treatment, often representing the optimal local therapy for palliation of pain, bleeding or edema.

3-D Conformal radiotherapy of localized prostate cancer within an Austrian-German multicenter trial: a prospective study of patients' acceptance of the rectal balloon during treatment.

PURPOSE: Patients with localized prostate cancer are treated with 3D radiotherapy using a rectal balloon catheter for internal immobilization of the prostate, thereby reducing the radiation dose to the dorsal rectal wall. The purpose of the study was to investigate clinical feasibility and the influence of acute rectal side effects and pre-existing hemorrhoids on patients' acceptance of the rectal balloon catheter. METHODS AND MATERIALS: 442 patients who underwent primary radiation therapy for localized prostate cancer were included in this prospective Austrian-German multicenter trial. The total radiation dose was either 70 Gy or 74 Gy. Acute rectal side effects were documented using the EORTC/RTOG grading score (European Organisation for Research and Treatment of Cancer/Radiation Therapy 225 Oncology Group) at weeks 2, 4 and 7 of radiation treatment. Within the same time intervals patients were interviewed about their tolerance of the rectal balloon catheter, evaluating five categories of acceptance (1 = no major complaints, 2 = pain at/during application, 3 = signs of blood at the balloon catheter after application but without any pain, 4 = signs of blood at the balloon catheter after application and pain, 5 = balloon application had to be stopped). Voluntary rectoscopy prior to radiotherapy was performed in 310 patients. RESULTS: 429/442 patients (97 %) were treated with the balloon catheter. No major complaints were reported in 79 % of the patients and no acute rectal side effects were seen in 52 % of the patients. Grade 1 side effects were seen in 31 % patients, Grade 2 in 17 % and Grade 3 in 0.5 %. Balloon use had to be stopped in only 4 % of the patients. There was significant correlation between balloon discomfort and rectal side effects (p < 0.01). The presence of hemorrhoids in 36 % patients prior to irradiation had no influence on balloon tolerance. CONCLUSIONS: The rectal balloon can be used in 3D radiotherapy of localized prostate cancer with a high degree of acceptance by the patients. Use of the balloon is safe within daily clinical treatment. Patients reporting acute rectal side effects experienced significantly more balloon discomfort, but the presence of hemorrhoids was not found to influence acceptance of the balloon.

3-D conformal radiotherapy of localized prostate cancer: a subgroup analysis of rectoscopic findings prior to radiotherapy and acute/late rectal side effects.

BACKGROUND AND PURPOSE: To identify endoscopic pathological findings prior to radiotherapy and a possible correlation with acute or chronic rectal side effects after three-dimensional conformal radiotherapy (3D-CRT) for prostate cancer. PATIENTS AND METHODS: Between 03/99 and 07/02, a total of 298 patients, who consented in a voluntary rectoscopy prior to radiotherapy were included into the analysis. Patients were treated with a total dose of either 70 or 74 Gy. Pathological rectoscopic findings like hemorrhoids, polyps or diverticula were documented. Acute and late rectal side effects were scored using the EORTC/RTOG score. RESULTS: The most frequent pathological endosopic findings were hemorrhoids (35%), polyps (24%) and diverticula (13%). Rectal toxicity was mostly low to moderate. Grade 0/1 cumulative acute and late rectal side effects were 82 and 84%, grade 2 were 18 and 17%, respectively. We could not identify any correlation between preexisting pathological findings and rectal side effects by statistical analysis. CONCLUSIONS: There is no evidence that prostate cancer patients presenting with endoscopic verified pathological findings in the rectal mucosa at diagnosis are at an increased risk to develop rectal side effects when treated with 3D-CRT of the prostatic region.

Synthesis and structure of K+ [iPrN=C=P]-, a 1-aza-3lambda3-phospha-3-allenide.

2-Isopropyl(trimethylsilyl)amino-1lambda3-phosphaalkyne 1 reacts with potassium tert-butoxide to form potassium 1-isopropyl-1-aza-3lambda3-phospha-3-allenide (2). This compound was structurally characterized as the corresponding 18-crown-6 ether complex 3. The molecular structure of 1 was also determined in order to compare the bonding situation in the anion and the neutral lambda3-phosphaalkyne. Compound 3 contains a nitrogen-carbon-phosphorus group for which the parameters were shown by X-ray structural analysis and quantum chemical calculations to lie between the extrema N-C[triple bond]P and N=C=P, suggesting reactivity typical of an ambident anion. This is indeed the case, as subsequent reaction of 2 with chlorotrimethylsilane at nitrogen regenerates the lambda3-phosphaalkyne 1; with chlorotriphenylsilane the new derivative 4 is formed. In contrast, chlorotrimethylstannane reacts at phosphorus, giving the 1-aza-3lambda3-phosphaallene isopropyliminomethylidene(trimethylstannyl)phosphane 5.

Stereotactic fractionated radiotherapy in patients with optic nerve sheath meningioma.

PURPOSE: To evaluate the effectiveness of stereotactic fractionated radiotherapy (SFRT) in the treatment of optic nerve sheath meningioma (ONSM). METHODS AND MARERIALS: Between 1994 and 2000, a total of 39 patients with either primary (n = 15) or secondary (n = 24) ONSM were treated with SFRT and received a median total tumor dose of 54 Gy using 1.8 Gy/fraction. RESULTS: The radiographic response to SFRT was documented in all patients as stable disease (no change) except for 1 patient with a partial response. After a median follow-up of 35.5 months, all patients with ONSM were alive without recurrence. The visual fields and visual acuity were improved in 6 of 15 and 1 of 16 examined eyes in patients with primary ONSM, respectively, and in 6 of 24 and 7 of 26 examined eyes in patients with secondary ONSM, respectively. Stable visual fields and visual acuity was observed in 8 of 14 and 15 of 16 patients with primary ONSM, respectively, and in 17 of 24 and 19 of 26 patients with secondary ONSM, respectively. Except for reversible alopecia and erythema, no other SFRT-related toxicity was observed. CONCLUSION: SFRT represents a very effective and low-toxic treatment modality for ONSM. Despite a median follow-up of 3 years, this series of primary ONSM holds promise for future studies. It adds substantial evidence that SFRT may definitely become a standard treatment approach in selected cases of ONSM.

Radiation therapy in the multimodal treatment approach of pituitary adenoma.

BACKGROUND: Pituitary tumors are relatively uncommon, comprising 10-12% of all intracranial tumors. The treatment consisting of surgery, radiotherapy and drug therapy or a combination of these modalities is aimed at the control of tumor cell proliferation and--in endocrine active tumors--the reduction of hormone secretion. However, the slow proliferation characteristics of pituitary tumors necessitate long-term studies for the evaluation of the treatment results. In the last decade there has been continuous improvement in surgical procedures, radiotherapy techniques and drug generation. In this paper, literature will be reviewed to assess the role of modern radiotherapy and radiosurgery in the management of pituitary adenomas. MATERIAL AND METHODS: Nowadays, magnetic resonance imaging for the definition of the target volume and a real three-dimensional (3-D) treatment planning with field conformation and the possibility for non-coplanar irradiation has to be recommended. Most groups irradiate these benign tumors with single doses of 1.8-2.0 Gy up to a total dose of 45 Gy or 50.4 Gy in extensive parasellar adenomas. Adenomas are mostly small, well circumscribed lesions, and have, therefore, attracted the use of stereotactically guided high-precision irradiation techniques which allow extreme focussing and provide steep dose gradients with selective treatment of the target and optimal protection of the surrounding brain tissue. RESULTS: Radiation therapy controls tumor growth in 80-98% of patients with non-secreting adenomas and 67-89% for endocrine active tumors. Reviewing the recent literature including endocrine active and non-secreting adenomas, irradiated postoperatively or in case of recurrence the 5-, 10- and 15-year local control rates amount 92%, 89% and 79%. In cases of microprolactinoma primary therapy consists of dopamine agonists. Irradiation should be preferred in patients with macroprolactinomas, when drug therapy and/or surgery failed or for patients medically unsuitable for surgery. Reduction and control of prolactin secretion can be achieved in 44-70% of patients. After radiotherapy in acromegaly patients somatomedin-C and growth hormone concentrations decrease to normal levels in 70-90%, with a decrease rate of 10-30% per year. Hypercortisolism is controlled in 50-83% of adults and 80% of children with Cushing's disease, generally in less than 9 months. Hypopituitarism is the most common side effect of pituitary irradiation with an incidence of 13-56%. Long-term overall risk for brain necrosis in a total of 1,388 analyzed patients was estimated to be 0.2%. Other side effects are rare too, and do also depend on the damage produced by tumor itself or preceding surgery. They include deterioration of vision in 1.7% of all cases, vascular changes in 6.3%, neuropsychological disorders such as dementia in 0.7% and secondary malignancies in 0.8%, if single doses of 2.0 Gy and total doses of 50 Gy are not exceeded. CONCLUSION: Conventional radiation therapy of pituitary adenoma is highly effective. It is recommended after subtotal resection of primary tumors such as macroadenomas, after gross total resection from endocrine active adenomas with postsurgical hormone secretion and for recurrent tumors. Radiosurgery seems to be a possible treatment alternative in experienced centers, and only in patients with adenomas smaller than 25-30 mm with a minimum distance of 2-3 mm to the chiasm.

Radiosurgery for brain metastases: the Tuebingen experience.

PURPOSE: To retrospectively investigate the effectiveness of linear accelerator based radiosurgery (RS) in the treatment of brain metastases (BM). MATERIAL AND METHODS: Of 55 patients with a total of 72 BM, 41 patients had a single brain metastasis and 14 patients had two or three metastases. Median tumour dose of 15Gy (range 8-20Gy) was prescribed to a median isodose surface of 90% (range 70-100%) encompassing the target volume. RESULTS: The median survival time (MST) for all 55 patients was 7 months [95% confidence interval (CI), 5-10 months] and 2-year survival is 18%. There was no significant difference between patients who had one brain metastasis and those with either two or three metastases (log rank P=0.7565). Multivariate analysis in patients with a single BM showed that interval between primary diagnosis (PD) to BM, maximum size of metastasis, and histology (renal cell carcinoma and melanoma versus others) were independent prognostic factors influencing survival. Local control was obtained in 66/72 (92%) metastases. Actuarial local control at 24 months was 52%. Only age (50 years) and histology (renal cell versus others) influenced local control in the univariate analysis in patients with a single BM. In multivariate analysis, size, histology (renal cell and melanoma versus others), activity of extracranial metastatic disease, age, interval from PD to BM and location (midline versus other) independently influenced local control, while the dose was not significant for our patient group. Only one patient developed radiographically suspected RS-induced necrosis after previous whole brain RT. CONCLUSION: RS was effective and little toxic in BM. Identification of prognostic factors must be performed to gain knowledge on patients most likely to benefit from this procedure.

Element-Element Bonds. IX.(1) Structures of Tetrakis(trifluoromethyl)diphosphane and -diarsane: Experimental and Theoretical Investigations.

X-ray structure determinations of tetrakis(trifluoromethyl)diphosphane (2c, mp -82 degrees C, triclinic, P&onemacr;; Z = 1, a = 529.7(3) pm, b = 681.6(2) pm, c = 802.8(3) pm, alpha = 108.58(1) degrees, beta = 99.66(1) degrees, gamma = 103.29(1) degrees, wR2 = 0.204) and -diarsane (3c, mp -52 degrees C, monoclinic, P2(1)/c; Z = 2, a = 769.5(3) pm, b = 750.0(3) pm, c = 960.7(2) pm, beta = 105.26(1) degrees, wR2 = 0.115), both at -100(3) degrees C, reveal the molecules to adopt the trans conformation in the solid. Compared with the tetramethyl derivatives, the E-E (224.6(2)/246.3(1) pm, E = P, As) and E-C (188.3(4)/201.3(7) pm) bonds are elongated by 4.5/4.8 pm and 3.4/3.4 pm, respectively. From gas electron diffraction studies of diphosphane 2c a mixture of 85(10)% trans and 15(10)% gauche conformers can be deduced; diarsane 3c shows the trans form exclusively. The molecular parameters (E-E, 224.8(11)/245.2(6); E-C, 189.6(4)/ 201.2(4) pm) agree excellently with those determined for the crystalline state. As a result of quantum chemical calculations at Hartree-Fock and hybrid density functional levels of theory using 6-311+G basis sets, the gauche conformer of hydrazine derivative 1c and the trans conformer of diarsane 3c are clearly lowest in energy. However, for diphosphane 2c the gauche and not the trans form is found to be slightly more stable. Variations of calculated E-E and E-C bond lengths are analyzed and compared with corresponding values of the parent compounds E(2)H(4) (1a to 3a) as well as the tetramethyl derivatives 1b to 3b.