Diagnosis and treatment of melanoma brain metastasis: a literature review.

BACKGROUND: Brain metastasis is common in patients with malignant melanoma and represents a significant cause of morbidity and mortality. Nearly 37% of patients with malignant melanoma eventually develop brain metastasis, and autopsy reports show that 75% of those who died of this disease developed brain metastasis. METHODS: We review the level I and level II evidence that guides indications for treatment with surgery, stereotactic radiosurgery, chemotherapy, and immunotherapy for patients with melanoma brain metastasis. RESULTS: Level I evidence supports the role of whole brain radiotherapy, microsurgery, and radiosurgery alone or in combination for the treatment of patients with melanoma brain metastasis. Chemotherapy has been ineffective. Ongoing studies continue to assess the effects of immunotherapy and agents in development. CONCLUSIONS: Brain metastasis is a common and formidable challenge in patients with malignant melanoma. Although there have been no randomized controlled trials exclusively in patients with melanoma brain metastasis, care can be guided by the application of level I evidence for the treatment of brain metastasis in general and phase II studies focusing specifically on melanoma brain metastasis. Promising new agents and approaches are needed and will hopefully be identified in the near future.

12 Gy gamma knife radiosurgical volume is a predictor for radiation necrosis in non-AVM intracranial tumors.

PURPOSE: To determine whether the 12-Gy radiosurgical volume (12-GyV) correlates with the development of postradiosurgical imaging changes suggestive of radiation necrosis in patients treated for non-arteriovenous malformation (non-AVM) intracranial tumors with gamma knife stereotactic radiosurgery (GKSRS). METHODS AND MATERIALS: A retrospective single-institution review of 129 patients with 198 separate non-AVM tumors was performed. Patients were followed with magnetic resonance imaging (MRI) and physical examinations at 3- to 6-month intervals. Patients who developed postradiosurgical MRI changes suggestive of radiation necrosis were labeled as having either symptomatic radiation necrosis (S-NEC) if they experienced any decline in neurologic examination associated with the imaging changes, or asymptomatic radiation necrosis (A-NEC) if they had a stable or improving neurologic examination. RESULTS: 12-GyV correlated with risk of S-NEC, which was 23% (for 12-GyV of 0-5 cc), 20% (5-10 cc), 54% (10-15 cc), and 57% (>15 cc). The risk of A-NEC did not significantly change with 12-GyV. Logistic regression analyses showed that the following factors were associated with the development of S-NEC: 12-GyV (p<0.01), occipital and temporal lesions (p<0.01), previous whole-brain radiotherapy (p=0.03), and male sex (p=0.03). Radiosurgical plan conformality did not correlate with the development of S-NEC. CONCLUSION: The risk of S-NEC, but not A-NEC after GKSRS for non-AVM tumors correlates with 12-GyV, and increases significantly for 12-GyV>0 cc.

Treatment of glomus jugulare tumors in patients with advanced age: planned limited surgical resection followed by staged gamma knife radiosurgery: a preliminary report.

OBJECTIVE: To minimize treatment comorbidities in glomus jugulare tumor patients with advanced age while reducing pulsatile tinnitus and preserving or improving residual hearing using a limited middle ear/mastoid tumor resection and postoperative gamma knife radiosurgery to tumor remnants in the jugular foramen region. STUDY DESIGN: Retrospective consecutive case review of five patients. SETTING: Tertiary referral, academic medical center. PATIENTS: Patients with advanced age (mean, 69.6 yr; range, 61-78 yr) harboring symptomatic glomus jugulare tumors. INTERVENTION: All patients were treated with resection of middle ear and mastoid portions of tumor and subsequent gamma knife radiosurgery to jugular foramen portion of tumor. MAIN OUTCOME MEASURES: Length of hospitalization; hearing, pulsatile tinnitus, cranial nerve, and tumor control status. RESULTS: All patients were treated on an outpatient surgical basis without the need for blood transfusion. There were no incidents of a change in cranial nerve status (Cranial Nerves VII, IX, X, XI, and XII) in the immediate postoperative period. All patients had improvement or resolution of pulsatile tinnitus with preservation or improvement of preoperative hearing levels. Tumor volume was stable or reduced in all patients at mean follow-up of 19 months (range, 11-24 mo). Gamma knife radiosurgery (mean peripheral dose of 15 Gy) was not associated with any significant immediate or delayed complications. CONCLUSION: Short-term data reveals that staged microsurgical and radiosurgical therapy for glomus jugulare tumors in the symptomatic patient with advanced age is safe and yields favorable results regarding tinnitus, hearing, and cranial nerve status. Long-term data are needed to further evaluate the effectiveness of this treatment algorithm before extrapolating this treatment option to younger patients.

Real-time inverse planning for Gamma Knife radiosurgery.

The challenges of real-time Gamma Knife inverse planning are the large number of variables involved and the unknown search space a priori. With limited collimator sizes, shots have to be heavily overlapped to form a smooth prescription isodose line that conforms to the irregular target shape. Such overlaps greatly influence the total number of shots per plan, making pre-determination of the total number of shots impractical. However, this total number of shots usually defines the search space, a pre-requisite for most of the optimization methods. Since each shot only covers part of the target, a collection of shots in different locations and various collimator sizes selected makes up the global dose distribution that conforms to the target. Hence, planning or placing these shots is a combinatorial optimization process that is computationally expensive by nature. We have previously developed a theory of shot placement and optimization based on skeletonization. The real-time inverse planning process, reported in this paper, is an expansion and the clinical implementation of this theory. The complete planning process consists of two steps. The first step is to determine an optimal number of shots including locations and sizes and to assign initial collimator size to each of the shots. The second step is to fine-tune the weights using a linear-programming technique. The objective function is to minimize the total dose to the target boundary (i.e., maximize the dose conformity). Results of an ellipsoid test target and ten clinical cases are presented. The clinical cases are also compared with physician's manual plans. The target coverage is more than 99% for manual plans and 97% for all the inverse plans. The RTOG PITV conformity indices for the manual plans are between 1.16 and 3.46, compared to 1.36 to 2.4 for the inverse plans. All the inverse plans are generated in less than 2 min, making real-time inverse planning a reality.

Phase II trial of radiosurgery to magnetic resonance spectroscopy-defined high-risk tumor volumes in patients with glioblastoma multiforme.

PURPOSE: To determine the efficacy of a Gamma Knife stereotactic radiosurgery (SRS) boost to areas of high risk determined by magnetic resonance spectroscopy (MRS) functional imaging in addition to standard radiotherapy for patients with glioblastoma (GBM). METHODS AND MATERIALS: Thirty-five patients in this prospective Phase II trial underwent surgical resection or biopsy for a GBM followed by SRS directed toward areas of MRS-determined high biological activity within 2 cm of the postoperative enhancing surgical bed. The MRS regions were determined by identifying those voxels within the postoperative T2 magnetic resonance imaging volume that contained an elevated choline/N-acetylaspartate ratio in excess of 2:1. These voxels were marked, digitally fused with the SRS planning magnetic resonance image, targeted with an 8-mm isocenter per voxel, and treated using Radiation Therapy Oncology Group SRS dose guidelines. All patients then received conformal radiotherapy to a total dose of 60 Gy in 2-Gy daily fractions. The primary endpoint was overall survival. RESULTS: The median survival for the entire cohort was 15.8 months. With 75% of recursive partitioning analysis (RPA) Class 3 patients still alive 18 months after treatment, the median survival for RPA Class 3 has not yet been reached. The median survivals for RPA Class 4, 5, and 6 patients were 18.7, 12.5, and 3.9 months, respectively, compared with Radiation Therapy Oncology Group radiotherapy-alone historical control survivals of 11.1, 8.9, and 4.6 months. For the 16 of 35 patients who received concurrent temozolomide in addition to protocol radiotherapeutic treatment, the median survival was 20.8 months, compared with European Organization for Research and Treatment of Cancer historical controls of 14.6 months using radiotherapy and temozolomide. Grade 3/4 toxicities possibly attributable to treatment were 11%. CONCLUSIONS: This represents the first prospective trial using selective MRS-targeted functional SRS combined with radiotherapy for patients with GBM. This treatment is feasible, with acceptable toxicity and patient survivals higher than in historical controls. This study can form the basis for a multicenter, randomized trial.

Radiosurgery for glomus jugulare tumors.

Glomus jugulare tumors arise from adventitial chemoreceptor tissue in the jugular bulb. Although histologically benign, these tumors can be locally aggressive because of their proximity to the lower cranial nerves and major vascular structures. Traditional treatment involves microsurgical removal with or without endovascular embolization, but morbidity following total resection can result in injury to the facial and lower cranial nerves. Radiosurgery has recently emerged as a promising alternative to older therapeutic strategies for treatment of glomus jugulare tumors. This article reviews the latest benefits of radiosurgery and demonstrates how this modality represents an effective treatment option for glomus jugulare tumors with excellent tumor control and low risk for morbidity. In addition, this article will detail the role of minimally invasive sub-total resection of glomus jugulare tumors as a surgical complement to gamma knife therapy.

The impact of a negative (111)indium-capromab pendetide scan before salvage radiotherapy.

PURPOSE: We determined the prognostic role, if any, of the ProstaScint (111)indium-capromab pendetide scan before salvage radiotherapy for biochemical recurrence after RP for localized prostate cancer. MATERIALS AND METHODS: We reviewed the records of 649 patients who underwent a ProstaScint scan from 1998 to 2004. A total of 44 patients were identified who had biochemical recurrence after RP and underwent a ProstaScint scan immediately before salvage radiotherapy. All patients received salvage radiotherapy to the prostatic bed unless pelvic lymph node uptake was identified on the scan, resulting in initial whole pelvic radiotherapy with 45 Gy, followed by a conformal boost to the prostate bed in 6. The median salvage radiotherapy dose to the prostate bed was 72 Gy. Patient demographics, pathological information, PSA values and ProstaScint results were collected retrospectively. The majority of ProstaScint scans were digitally fused with noncontrast pelvic computerized tomography images for interpretation. PSA progression after radiotherapy was defined using American Society for Therapeutic Radiation and Oncology criteria. RESULTS: At a mean followup of 22 months 43 of 44 patients (97%) experienced a PSA decrease after salvage radiotherapy with a mean PSA nadir of 0.16 ng/ml compared to a mean pre-radiotherapy PSA of 1.7 ng/ml. Of the 44 patients 15 (34%) showed post-radiotherapy PSA progression. When the entire cohort was analyzed, patients with negative ProstaScint scans had statistically lower post-radiotherapy PSA progression rates than patients with positive scans (1 of 10 or 10% vs 14 of 34 or 41%, p = 0.026). Patients with negative ProstaScint results were also statistically more likely to have a pre-radiotherapy PSA of less than 1.0 ng/ml (p = 0.005), no seminal vesicle involvement (p = 0.006), a greater mean PSA doubling time (p = 0.008) and received no hormone therapy (p = 0.003). When patients with pre-radiotherapy PSA less than 1.0 ng/ml were analyzed, a negative ProstaScint scan suggested but did not provide a statistically significant advantage over pre-radiotherapy PSA alone for predicting post-radiotherapy PSA progression (1 of 9 or 11% for negative vs 5 of 15 or 33% for positive scans, p = 0.20). CONCLUSIONS: Our early experience supports an improved prognosis in patients receiving salvage pelvic radiotherapy for biochemical recurrence after RP who have a negative pre-radiotherapy ProstaScint scan. However, this finding is not necessarily independent of pre-radiotherapy PSA.

A novel computer based expert decision making model for prostate cancer disease management.

PURPOSE: We propose a strategic, computer based, prostate cancer decision making model based on the analytic hierarchy process. We developed a model that improves physician-patient joint decision making and enhances the treatment selection process by making this critical decision rational and evidence based. MATERIALS AND METHODS: Two groups (patient and physician-expert) completed a clinical study comparing an initial disease management choice with the highest ranked option generated by the computer model. Participants made pairwise comparisons to derive priorities for the objectives and subobjectives related to the disease management decision. The weighted comparisons were then applied to treatment options to yield prioritized rank lists that reflect the likelihood that a given alternative will achieve the participant treatment goal. Aggregate data were evaluated by inconsistency ratio analysis and sensitivity analysis, which assessed the influence of individual objectives and subobjectives on the final rank list of treatment options. RESULTS: Inconsistency ratios less than 0.05 were reliably generated, indicating that judgments made within the model were mathematically rational. The aggregate prioritized list of treatment options was tabulated for the patient and physician groups with similar outcomes for the 2 groups. Analysis of the major defining objectives in the treatment selection decision demonstrated the same rank order for the patient and physician groups with cure, survival and quality of life being more important than controlling cancer, preventing major complications of treatment, preventing blood transfusion complications and limiting treatment cost. Analysis of subobjectives, including quality of life and sexual dysfunction, produced similar priority rankings for the patient and physician groups. Concordance between initial treatment choice and the highest weighted model option differed between the groups with the patient group having 59% concordance and the physician group having only 42% concordance. CONCLUSIONS: This study successfully validated the usefulness of a computer based prostate cancer management decision making model to produce individualized, rational, clinically appropriate disease management decisions without physician bias.