Radiocirurgia

Abstract Development of hypofractionated stereotactic radiosurgery (HSRS) has expanded the size of lesion that can be safely treated by focused radiation in a limited number of treatment sessions. However, clinical data regarding the efficacy and morbidity of HSRS in the treatment of cerebral metastasis is lacking. Here, we review our experience with CyberKnife® HSRS for this indication. From 2005 to 2010, we identified 37 patients with large (>3 cm in diameter) cerebral metastases resection cavity that was treated with HSRS. This constituted approximately 8% of all treated resection cavities. We reviewed dose regimens, local control, distal control, and treatment associated morbidities. Primary sites for the metastatic lesions included: lung (n = 10), melanoma (n = 12), breast (n = 9), kidney (n = 4), and colon (n = 2). All patients underwent resection of the cerebral metastasis and received 800 cGy × 3 daily fractions to the resection cavity. Of the 37 patients treated, one-year follow-up data was available for 35 patients. The median survival was 5.5 months. Actuarial local control rate at 6 months was 80%. Local failures did not correlate with prior WBRT, or tumor histology. Distant recurrence occurred in 7 of the 35 patients. Morbidities associated with HSRS totaled 9%, including radiation necrosis (n = 1, 2.9%), prolonged steroid use (n = 1, 2.9%), and new-onset seizures (n = 1, 2.9%). This study demonstrates the safety and efficacy of an 800 cGy × 3 daily fractions CyberKnife® HSRS regimen for irradiation of large resection cavity. The efficacy compares favorably to historical data derived from patients undergoing WBRT, SRS, or brachytherapy.

• Content Type Journal Article
• Category Clinical Study – Patient Study
• Pages 1-10
• DOI 10.1007/s11060-011-0697-z
• Authors
  • Che-Chuan Wang, Department of Neurosurgery, Chi Mei Medical Center, Tainan, Taiwan
  • Scott R. Floyd, Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Boston, MA, USA
  • Chin-Hong Chang, Department of Neurosurgery, Chi Mei Medical Center, Tainan, Taiwan
  • Peter C. Warnke, Division of Neurosurgery, University of Chicago Medical Center, Chicago, IL, USA
  • Chung-Ching Chio, Department of Neurosurgery, Chi Mei Medical Center, Tainan, Taiwan
  • Ekkehard M. Kasper, Division of Neurosurgery, Beth Israel Deaconess Medical Center, Boston, MA, USA
  • Anand Mahadevan, Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Boston, MA, USA
  • Eric T. Wong, Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA, USA
  • Clark C. Chen, Division of Neurosurgery, University of California, San Diego 3855 Health Science Drive, #0987, La Jolla, CA 92093-0987, USA

• Journal Journal of Neuro-Oncology
• Online ISSN 1573-7373
• Print ISSN 0167-594X

http://www.springerlink.com/content/045472457r44v32g/

Journal of Neurosurgery: Spine, Volume 0, Issue 0, Page 1-5, Ahead of Print.

Renee M. Reynolds, M.D., Elizabeth Boswell, M.D., Christine M. Hulette, M.D., Thomas J. Cummings, M.D., Michael M. Haglund, M.D., Ph.D., Elizabeth Boswell, M.D., Christine M. Hulette, M.D., Thomas J. Cumm ings, M.D., and Michael M. Haglund, M.D.Ph.D. In this paper the authors describe the rare disorder of diffuse leptomeningeal oligodendrogliomatosis in a patient with an oligodendroglioma of the cauda equina who died suddenly. Reviewing this uncommon pathological entity is important so that it can be recognized and treated appropriately. This young, otherwise healthy woman with initial symptoms of low-back pain had a mass lesion of the cauda equina. During a workup, profound refractory intracranial hypertension suddenly developed despite aggressive surgical and medical intervention. Autopsy revealed a spinal cord oligodendroglioma with diffuse leptomeningeal oligodendrogliomatosis of the brain and spinal cord. Given the unforeseen outcome in this patient, this entity, although rare, should be considered in patients with similar presentations and addressed early to prevent similar outcomes. A review of the details of this case as well as the literature is presented below.

http://thejns.org/doi/abs/10.3171/2011.7.SPINE10728?ai=rt&mi=0&af=R

Abstract

BACKGROUND:

To perform a meta-analysis on newly diagnosed brain metastases patients treated with whole-brain radiotherapy (WBRT) and stereotactic radiosurgery (SRS) boost versus WBRT alone, or in patients treated with SRS alone versus WBRT and SRS boost.

METHODS:

The meta-analysis primary outcomes were overall survival (OS), local control (LC), and distant brain control (DBC). Secondary outcomes were neurocognition, quality of life (QOL), and toxicity. Using published Kaplan-Meier curves, results were pooled using hazard ratios (HR).

RESULTS:

Two RCTs reported on WBRT and SRS boost versus WBRT alone. For multiple brain metastases (2-4 tumors) we conclude no difference in OS, and LC significantly favored WBRT plus SRS boost. Three RCTs reported on SRS alone versus WBRT plus SRS boost (1-4 tumors). There was no difference in OS despite both LC and DBC significantly favoring WBRT plus SRS boost. Although secondary endpoints could not be pooled for meta-analysis, those RCTs evaluating SRS alone conclude better neurocognition using the validated Hopkins Verbal Learning Test, no adverse risk in deteriorating Mini-Mental Status Exam scores or in maintaining performance status, and fewer late toxicities. We conclude insufficient data for QOL outcomes.

CONCLUSIONS:

For selected patients, we conclude no OS benefit for WBRT plus SRS boost compared with SRS alone. Although additional WBRT improves DBC and LC, SRS alone should be considered a routine treatment option due to favorable neurocognitive outcomes, less risk of late side effects, and does not adversely affect the patients performance status. Cancer 2011. © 2011 American Cancer Society.

http://dx.doi.org/10.1002%2Fcncr.26515

Abstract Leptomeningeal metastasis is a devastating complication of the central nervous system in patients with late-stage solid or hematological cancers. Leptomeningeal metastasis results from the multifocal seeding of the leptomeninges by malignant cancer cells. Although central nervous system metastasis usually presents in patients with widely disseminated and progressive late-stage cancer, malignant cells may spread to the cerebrospinal fluid during earlier disease stages in particularly aggressive cancers. Treatment of leptomeningeal metastasis is largely palliative but will often provide stabilization and protection from further neurological deterioration and improve quality of life. There is a need to raise awareness of the impact of leptomeningeal metastases on cancer patients and its known and putative biological basis. Novel diagnostic approaches include identification of biomarkers that may stratify the risk for developing leptomeningeal metastasis. Current therapies can be used more effectively while waiting for advanced treatments to be developed.

• Content Type Journal Article
• Category Topic Review
• Pages 1-10
• DOI 10.1007/s11060-011-0686-2
• Authors
  • Jai Grewal, Long Island Brain Tumor Center, NSPC, 600 Northern Blvd, Suite 113, Great Neck, NY 11577, USA
  • Marlon Garzo Saria, Department of Neurosciences, Moores UCSD Cancer Center, UC San Diego, La Jolla, CA 92093, USA
  • Santosh Kesari, Department of Neurosciences, Moores UCSD Cancer Center, UC San Diego, La Jolla, CA 92093, USA

• Journal Journal of Neuro-Oncology
• Online ISSN 1573-7373
• Print ISSN 0167-594X

http://www.springerlink.com/content/y711p22448606055/

Abstract Brain metastases (BM) are treated with surgical resection when feasible. Unfortunately this occurs only in a small subset of patients. The optimal treatment for patients with intracranial metastases non amenable to surgical resection has not been identified. Radiotherapy improves symptom control and survival but long-term local control has been poor. Conventional chemotherapies have generally produced disappointing results possibly due to their limited ability to penetrate the blood brain barrier. Therefore, newer treatments are required for patients with unresectable BM. Targeted therapies such as bevacizumab, erlotinib, gefitinib, sunitinib and sorafenib, are all licensed and have demonstrated improved survival in patients with metastatic disease. In this review we will present current data on targeted therapies that have been approved for the treatment of malignant tumours and we discuss the evidence of their use in patients with BM.

• Content Type Journal Article
• Pages 1-8
• DOI 10.1007/s11060-011-0661-y
• Authors
  • Dionysis Papadatos-Pastos, Royal Marsden Hospital, Sutton, UK
  • Udai Banerji, Royal Marsden Hospital, Sutton, UK

• Journal Journal of Neuro-Oncology
• Online ISSN 1573-7373
• Print ISSN 0167-594X

http://www.springerlink.com/content/jx0vg42128881384/

Abstract Medulloblastoma (MB) is the most common malignant primary brain tumour in childhood. Metastatic disease (M+) at diagnosis is the most important negative prognostic clinical marker and, despite craniospinal irradiation and intensive chemotherapy, it remains one of the leading causes of treatment failure. To date, few clinical and biological data have been evaluated to obtain an additional prognostic profile for these high-risk patients. In this study, 169 patients with metastatic MB registered in the multicentre HIT2000 trial of the German Society of Pediatric Oncology and Haematology (GPOH) have been investigated to determine the importance of p53 protein expression in predicting survival. At a median follow-up of 4.1 years, 159 patients with p53-negative tumours had significantly better four-year event-free survival (EFS) and progression-free survival (PFS) (56 ± 11, 59 ± 4%) than 10 patients with p53-positive tumours (40 ± 16, 40 ± 16%; P = 0.018 for EFS, P = 0.007 for PFS, respectively). Furthermore, four-year overall survival (OS) of children with p53-negative tumours was higher than for children with p53-positive tumours (72 ± 4 vs. 35 ± 18%, P = 0.05). Three of the p53-positive MBs harbored a point mutation in the TP53 gene. p53 protein assessment by immunohistochemistry may be a useful tool for sub-stratification of metastatic high-risk MB patients.

• Content Type Journal Article
• Pages 1-7
• DOI 10.1007/s11060-011-0648-8
• Authors
  • Marco Gessi, Institute of Neuropathology, University of Bonn Medical Center, Sigmund-Freud-Strasse 25, 53127 Bonn, Germany
  • André O. von Bueren, Department of Pediatric Haematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
  • Stefan Rutkowski, Department of Pediatric Haematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
  • Torsten Pietsch, Institute of Neuropathology, University of Bonn Medical Center, Sigmund-Freud-Strasse 25, 53127 Bonn, Germany

• Journal Journal of Neuro-Oncology
• Online ISSN 1573-7373
• Print ISSN 0167-594X

http://www.springerlink.com/content/dt51102g420526n0/

Carsten Nieder, Minesh P Mehta
Radiation Oncology 2009, 4:10 (4 March 2009)

Background

This review addresses the strengths and weaknesses of 6 different prognostic indices, published since the Radiation Therapy Oncology Group (RTOG) developed and validated the widely used 3-tiered prognostic index known as recursive partitioning analysis (RPA) classes, i.e. between 1997 and 2008. In addition, other analyses of prognostic factors in groups of patients, which typically are underrepresented in large trials or databases, published in the same time period are reviewed.

Methods

Based on a systematic literature search, studies with more than 20 patients were included. The methods and results of prognostic factor analyses were extracted and compared. The authors discuss why current data suggest a need for a more refined index than RPA.

Results

So far, none of the indices has been derived from analyses of all potential prognostic factors. The 3 most recently published indices, including the RTOG’s graded prognostic assessment (GPA), all expanded from the primary 3-tiered RPA system to a 4-tiered system. The authors’ own data confirm the results of the RTOG GPA analysis and support further evaluation of this tool.

Conclusion

This review provides a basis for further refinement of the current prognostic indices by identifying open questions regarding, e.g., performance of the ideal index, evaluation of new candidate parameters, and separate analyses for different cancer types. Unusual primary tumors and their potential differences in biology or unique treatment approaches are not well represented in large pooled analyses.

http://www.ro-journal.com/content/4/1/10

Salvador Villà, Damien C Weber, Cristina Moretones, Anabel Mañes, Christophe Combescure, Josep Jové, Paloma Puyalto, Patricia Cuadras, Jordi Bruna, Eugènia Verger, Carme Balañà, Francesc Graus
Radiation Oncology 2011, 6:23 (2 March 2011)

Abstract

Background

Prognostic indexes are useful to guide tailored treatment strategies for cancer patients with brain metastasis (BM). We evaluated the new Graded Prognostic Assessment (GPA) scale in a prospective validation study to compare it with two published prognostic indexes.

Methods

A total of 285 newly diagnosed BM (n = 85 with synchronous BM) patients, accrued prospectively between 2000 and 2009, were included in this analysis. Mean age was 62 ± 12.0 years. The median KPS and number of BM was 70 (range, 20-100) and 3 (range, 1-50), respectively. The majority of primary tumours were lung (53%), or breast (17%) cancers. Treatment was administered to 255 (89.5%) patients. Only a minority of patients could be classified prospectively in a favourable prognostic class: GPA 3.5-4: 3.9%; recursive partitioning analysis (RPA) 1, 8.4% and Basic Score for BM (BSBM) 3, 9.1%. Mean follow-up (FU) time was 5.2 ± 4.7 months.

Results

During the period of FU, 225 (78.9%) patients died. The 6 months- and 1 year-OS was 36.9% and 17.6%, respectively. On multivariate analysis, performance status (P < 0.001), BSBM (P < 0.001), Center (P = 0.007), RPA (P = 0.02) and GPA (P = 0.03) were statistically significant for OS. The survival prediction performances’ of all indexes were identical. Noteworthy, the significant OS difference observed within 3 months of diagnosis between the BSBM, RPA and GPA classes/groups was not observed after this cut-off time point. Harrell’s concordance indexes C were 0.58, 0.61 and 0.58 for the GPA, BSBM and RPA, respectively.

Conclusions

Our data suggest that the new GPA index is a valid prognostic index. In this prospective study, the prediction performance was as good as the BSBM or RPA systems. These published indexes may however have limited long term prognostication capability.

http://www.ro-journal.com/content/6/1/23

Giuseppe Minniti, Enrico Clarke, Gaetano Lanzetta, Mattia F Osti, Guido Trasimeni, Alessandro Bozzao, Andrea Romano, Riccardo M Enrici
Radiation Oncology 2011, 6:48 (15 May 2011)

Purpose

to investigate the factors affecting survival and toxicity in patients treated with stereotactic radiosurgery (SRS), with special attention to volumes of brain receiving a specific dose (V10 – V16 Gy) as predictors for brain radionecrosis.

Patients and Methods

Two hundred six consecutive patients with 310 cerebral metastases less than 3.5 cm were treated with SRS as primary treatment and followed prospectively at University of Rome La Sapienza Sant’Andrea Hospital. Overall survival, brain control, and local control were estimated using the Kaplan-Meier method calculated from the time of SRS. Univariate and multivariate analysis using a Cox proportional hazards regression model were performed to determine the predictive value of prognostic factors for treatment outcome and SRS-related complications.

Results

Median overall survival and brain control were 14.1 months and 10 months, respectively. The 1-year and 2-year survival rates were 58% and 24%, and respective brain control were 43% and 22%. Sixteen patients recurred locally after SRS, with 1-year and 2-year local control rates of 92% and 84%, respectively. On multivariate analysis, stable extracranial disease and KPS >70 were associated with the most significant survival benefit. Neurological complications were recorded in 27 (13%) patients. Severe neurological complications (RTOG Grade 3 and 4) occurred in 5.8% of patients. Brain radionecrosis occurred in 24% of treated lesions, being symptomatic in 10% and asymptomatic in 14%. On multivariate analysis, V10 through V16 Gy were independent risk factors for radionecrosis, with V10 Gy and V12 Gy being the most predictive (p = 0.0001). For V10 Gy >12.6 cm3 and V12 Gy >10.9 cm3 the risk of radionecrosis was 47%.

Conclusions

SRS alone represents a feasible option as initial treatment for patients with brain metastases, however a significant subset of patients may develop neurological complications. Lesions with V12 Gy >8.5 cm3 carries a risk of radionecrosis >10% and should be considered for hypofractionated stereotactic radiotherapy especially when located in/near eloquent areas.

http://www.ro-journal.com/content/6/1/48