C. Leland Rogers

Short Delay in Initiation of Radiotherapy May Not Affect Outcome of Patients With Glioblastoma: A Secondary Analysis From the Radiation Therapy Oncology Group Database

PURPOSE To analyze the Radiation Therapy Oncology Group (RTOG) database of patients with glioblastoma and appraise whether outcome was influenced by time to initiation of radiation therapy (RT). PATIENTS AND METHODS From 1974 through 2003, adult patients with histologically confirmed supratentorial glioblastoma were enrolled onto 16 RTOG studies. Of 3,052 enrolled patients, 197 patients (6%) were either initially rendered ineligible or had insufficient chronologic data, leaving a cohort of 2,855 patients for the present analysis. We selected four patient groups based on the interval from surgery to the start of RT: <or= 2 weeks, 2 to 3 weeks, 3 to 4 weeks, more than 4 weeks to the protocol eligibility limit of 6 weeks. Survival times were estimated by the Kaplan-Meier method. Multivariate analysis incorporated variables of time interval, recursive partitioning analysis (RPA) class, and treatment regimen. RESULTS No decrement in survival could be identified with increasing time to initiation of RT. Among our four temporal groupings, median survival time was unexpectedly and significantly greater in the group with the longest interval (> 4 weeks) than in those with the shortest delay (<or= 2 weeks): respectively, 12.5 months versus 9.2 months (P < .0001). On multivariate analysis, with overall survival as the end point, time interval more than 4 weeks and lower RPA class were both significant predictors of improved outcome. Treatment regimen was not a significant factor. CONCLUSION There is no evident reduction in survival by delaying initiation of RT within the relatively narrow constraint of 6 weeks. An unanticipated yet significantly superior outcome was identified for patients for whom RT was delayed beyond 4 weeks from surgery.

Long-term pain response and quality of life in patients with typical trigeminal neuralgia treated with gamma knife stereotactic radiosurgery.

OBJECTIVEThe long-term outcome of patients treated with gamma knife radiosurgery (GKRS) for typical trigeminal neuralgia has not been fully studied. We evaluated 185 patients who underwent their first GKRS treatment between 1997 and 2003 at the Barrow Neurological Institute. METHODSFollow-up was obtained by surveys and review of medical records. Outcomes were assessed by the Barrow Neurological Institute Pain Intensity Score and Brief Pain Inventory. The most common maximum dose was 80 Gy targeted at the root entry zone. Outcomes are presented for the 136 (74%) patients for whom more than 4 years of clinical follow-up data were obtained. RESULTSTreatment failed in 33% of the cohort within 2 years, but only an additional 1% relapsed after 4 years. Actuarial analysis demonstrated that 32% of patients were pain-free off medication and 63% had at least a good outcome at 7 years. When GKRS was used as the primary treatment, 45% of the patients were pain-free at 7 years. In contrast, 10% of patients in whom previous treatment had failed were pain-free. When needed, salvage therapy with repeat GKRS, microvascular decompression, or percutaneous lesioning was successful in 70%. Posttreatment facial numbness was reported as very bothersome in 5%, most commonly in patients who underwent another invasive treatment. After GKRS, 73% reported that trigeminal neuralgia had no impact on their quality of life. CONCLUSIONGKRS is a reasonable long-term treatment option for patients with typical trigeminal neuralgia. It yields durable pain control in a majority of patients, as well as improved quality of life with limited complications and it does not significantly affect the efficacy of other surgical treatments, should they be needed.

American College of Radiology appropriateness criteria on multiple brain metastases.

EXPERT PANEL ON RADIATION ONCOLOGY–BRAIN METASTASES; GREGORY M. M. VIDETIC, M.D.,* LAURIE E. GASPAR, M.D., M.B.A.,y AMR M. AREF, M.D.,z ISABELLE M. GERMANO, M.D.,x BRIAN J. GOLDSMITH, M.D.,k JOSEPH P. IMPERATO, M.D.,{ KAREN J. MARCUS, M.D., MICHAEL W. MCDERMOTT, M.D.,** MARK W. MCDONALD, M.D.,yy ROY A. PATCHELL, M.D.,zz H. IAN ROBINS, M.D., PH.D.,xx C. LELAND ROGERS, M.D.,kk JOHN H. SUH, M.D.,* AARON H. WOLFSON, M.D.,{{ AND FRANZ J. WIPPOLD, II, M.D.

ACR Appropriateness Criteria®: Single Brain Metastasis

Single brain metastasis represents a common neurologic complication of cancer. Given the number of treatment options that are available for patients with brain metastasis and the strong opinions that are associated with each option, appropriate treatment for these patients has become controversial. Prognostic factors such as recursive partitioning analysis and graded prognostic assessment can help guide treatment decisions. Surgery, whole brain radiation therapy (WBRT), stereotactic radiosurgery or combination of these treatments can be considered based on a number of factors. Despite Class I evidence suggestive of best therapy, the treatment recommendation is quite varied among physicians as demonstrated by the American College of Radiologys Appropriateness Panel on single brain metastasis. Given the potential concerns of the neurocognitive effects of WBRT, the use of SRS alone or SRS to a resection cavity has gained support. Since aggressive local therapy is beneficial for survival, local control and quality of life, the use of these various treatment modalities needs to be carefully investigated given the growing number of long-term survivors. Enrollment of patients onto clinical trials is important to advance our understanding of brain metastasis.

Pathology concordance levels for meningioma classification and grading in NRG Oncology RTOG Trial 0539

BACKGROUND With advances in the understanding of histopathology on outcome, accurate meningioma grading becomes critical and drives treatment selection. The 2000 and 2007 WHO schema greatly increased the proportion of grade II meningiomas. Although associations with progression-free survival (PFS) and overall survival (OS) have been independently validated, interobserver concordance has not been formally assessed. METHODS Once mature, NRG Oncology RTOG-0539 will report PFS and OS in variably treated low-, intermediate-, and high-risk cohorts. We address concordance of histopathologic assessment between enrolling institutions and central review, performed by a single pathologist (AP), who is also involved in developing current WHO criteria. RESULTS The trial included 170 evaluable patients, 2 of whom had 2 eligible pathology reviews from different surgeries, resulting in 172 cases for analysis. Upon central review, 76 cases were categorized as WHO grade I, 71 as grade II, and 25 as grade III. Concordance for tumor grade was 87.2%. Among patients with WHO grades I, II, and III meningioma, respective concordance rates were 93.0%, 87.8%, and 93.6% (P values < .0001). Moderate to substantial agreement was encountered for individual grading criteria and were highest for brain invasion, ≥20 mitoses/10 high-powered field [HPF], and spontaneous necrosis, and lowest for small cells, sheeting, and ≥4 mitoses/10 HPF. In comparison, published concordance for gliomas in clinical trials have ranged from 8%-74%. CONCLUSION Our data suggest that current meningioma classification and grading are at least as objective and reproducible as for gliomas. Nevertheless, reproducibility remains suboptimal. Further improvements may be anticipated with education and clarification of subjective criteria, although development of biomarkers may be the most promising strategy.

Opportunities for clinical research in meningioma

Meningiomas, when benign, are commonly treated with surgical resection alone. However, the optimal treatment for patients with subtotally resected or recurrent World Health Organization (WHO) grade I tumors, or WHO grade II and III tumors, regardless of the extent of resection, is not well defined, with both a paucity of high quality published evidence as well as a perceived minimal clinical effect for currently available interventions, specifically in terms of prolonging survival. In consideration of the size of the patient population with incompletely treated or non-benign meningiomas, there are opportunities for conducting high quality, prospective, multicenter clinical trials. In this review, we discuss a number of trials that were attempted and/or completed by cooperative groups or clinical consortia, and describe areas of clearly unmet need in terms of defining the optimal treatment regimens. Finally, we discuss ongoing efforts to develop new trials to more definitively address important therapeutic questions.

Patient autonomy and shared decision making in the management of urethral cancer

Department of Radiation Oncology, Virginia Commonwealth University, Massey Cancer Center, Richmond, Virginia Radiation Oncology Service, Hunter Holmes McGuire VA Medical Center, Richmond, Virginia Department of Radiation Oncology, Indiana University, IU Health Arnett Cancer Center, Lafayette, Indiana Hematology Oncology Section, Medical Service, Hunter Holmes McGuire VA Medical Center, Richmond, Virginia Division ofHematology,Oncology andPalliative Care, VirginiaCommonwealthUniversity,MasseyCancerCenter, Richmond, Virginia Department of Urology, Virginia Commonwealth University, Richmond, Virginia Department of Urology, Hunter Holmes McGuire VA Medical Center, Richmond, Virginia Department of Radiology, Hunter Holmes McGuire VA Medical Center, Richmond, Virginia

Meningioma—Viewpoint: Fractionated Radiotherapy

Fractionated radiation therapy (RT) is frequently used in the treatment of intracranial meningioma, either as a primary treatment, or more frequently, as an adjunct therapy. Benign intracranial meningiomas, despite being generally noninvasive and slow-growing, frequently occupy intracranial locations that make surgical interventions potentially morbid or preclude the use of single-fraction radiosurgery because of the proximity to critical neural structures. Fractionated RT permits safe treatment of such lesions with excellent therapeutic outcomes, often with minimal morbidity. Atypical and malignant meningiomas, characterized by their more aggressive clinical course and unfavorable histological features, benefit from the use of adjuvant fractionated therapy to reduce recurrence rates and delay progression of disease. This chapter reviews the role of fractionated RT in the management of intracranial meningioma; the role or radiosurgery is discussed in a separate chapter.