Phase I Trial of Stereotactic Body Radiation Therapy Dose Escalation in Pancreatic Cancer.

PURPOSE: Stereotactic body radiation therapy (SBRT) has demonstrated encouraging local tumor control rates in the treatment of pancreatic cancer, yet we lack prospective clinical trials evaluating dose-escalation strategies among patients treated with 5-fraction SBRT. This phase 1 dose-escalation trial was conducted to determine the maximum tolerated dose of SBRT in patients with pancreatic cancer. METHODS AND MATERIALS: Thirty patients with pancreatic cancer were enrolled and treated with 40, 45, or 50 Gy SBRT in 5 fractions with doses determined using a time-to-event continual reassessment method trial design. Systemic therapy was permitted before and after SBRT, but not mandated by the study protocol. Toxicity was the primary study endpoint, and any grade ≥3 acute or late toxicity potentially attributable to SBRT was considered a dose-limiting toxicity. Secondary endpoints included local progression, distant progression, and overall survival. RESULTS: The median follow up from SBRT was 8.9 months (range, 1.7-62.6 months). Nineteen patients (63%) had locally advanced disease, 3 patients (10%) had metastatic disease, and 8 patients (27%) had medically unresectable disease. Three patients (10%) received 40 Gy, 16 patients (53%) received 45 Gy, and 11 patients (37%) received 50 Gy. Seven patients (23%) experienced grade ≤2 acute toxicity, and 2 patients (6.7%) experienced grade 4 to 5 late toxicity, both of which occurred in the 45 Gy group. Median survival time was 17.1 months from the time of diagnosis and 9.8 months from SBRT. The 1-year cumulative incidence of local progression was 14.2% (95% confidence interval, 4.2%-30%). CONCLUSIONS: This dose-escalation trial evaluated high-dose SBRT delivered in 5 fractions, and overall demonstrated favorable local control and survival, but was associated with nontrivial rates of severe late gastrointestinal toxicity potentially attributable to radiation. Further prospective studies are needed to define the safety and efficacy of high-dose SBRT in patients with pancreatic cancer.

Claims-Based Approach to Predict Cause-Specific Survival in Men With Prostate Cancer.

PURPOSE: Treatment decisions about localized prostate cancer depend on accurate estimation of the patient's life expectancy. Current cancer and noncancer survival models use a limited number of predefined variables, which could restrict their predictive capability. We explored a technique to create more comprehensive survival prediction models using insurance claims data from a large administrative data set. These data contain substantial information about medical diagnoses and procedures, and thus may provide a broader reflection of each patient's health. METHODS: We identified 57,011 Medicare beneficiaries with localized prostate cancer diagnosed between 2004 and 2009. We constructed separate cancer survival and noncancer survival prediction models using a training data set and assessed performance on a test data set. Potential model inputs included clinical and demographic covariates, and 8,971 distinct insurance claim codes describing comorbid diseases, procedures, surgeries, and diagnostic tests. We used a least absolute shrinkage and selection operator technique to identify predictive variables in the final survival models. Each model's predictive capacity was compared with existing survival models with a metric of explained randomness (ρ2) ranging from 0 to 1, with 1 indicating an ideal prediction. RESULTS: Our noncancer survival model included 143 covariates and had improved survival prediction (ρ2 = 0.60) compared with the Charlson comorbidity index (ρ2 = 0.26) and Elixhauser comorbidity index (ρ2 = 0.26). Our cancer-specific survival model included nine covariates, and had similar survival predictions (ρ2 = 0.71) to the Memorial Sloan Kettering prediction model (ρ2 = 0.68). CONCLUSION: Survival prediction models using high-dimensional variable selection techniques applied to claims data show promise, particularly with noncancer survival prediction. After further validation, these analyses could inform clinical decisions for men with prostate cancer.

Differences in United States Insurance Payer Policies and American Society for Radiation Oncology's (ASTRO) Model Policy on Stereotactic Body Radiation Therapy (SBRT).

PURPOSE: Insurance payers in the United States vary in the indications for which they consider stereotactic body radiation therapy (SBRT) "medically necessary." We compared changes in policies after the last update to the American Society for Radiation Oncology's (ASTRO) SBRT model policy. METHODS AND MATERIALS: We identified 77 payers with SBRT policies in 2015 from a policy aggregator, as well as 4 national benefits managers (NBMs). Of these, 65 payers and 3 NBMs had publicly available updates since 2015. For each of the indications in ASTRO's model policy, we calculated the proportion of payers that considered SBRT medically necessary. We used Fisher's exact test to compare these proportions between 2015 and now, between policies updated in the past 12 months and those updated less often, and between national and regional payers currently. RESULTS: Payers consider SBRT medically necessary most often for primary lung cancer (97%), reirradiation to the spine (91%), prostate cancer (68%), primary liver cancer (66%), and spinal metastases with radioresistant histologies (66%). Policies have become more aligned with ASTRO's model policy over time. National payers and NBMs cover indications in higher proportions than regional payers. CONCLUSIONS: Although there have been improvements over time, more work is needed to align payer policies with ASTRO's model SBRT policy, especially at the regional level.

The Impact of Surgeons on the Likelihood of Mastectomy in Breast Cancer.

OBJECTIVE: This study evaluates the impact of individual surgeons and institutions on the use of mastectomy or breast conserving surgery (BCS) among elderly women with breast cancer. SUMMARY OF BACKGROUND DATA: Current literature characterizes patient clinical and demographic factors that increase likelihood of mastectomy use. However, the impact of the individual provider or institution is not well understood, and could provide key insights to biases in the decision-making process. METHODS: A retrospective cohort study of 29,358 women 65 years or older derived from the SEER-Medicare linked database with localized breast cancer diagnosed from 2000 to 2009. Multilevel, multivariable logistic models were employed, with odds ratios (ORs) used to describe the impact of demographic or clinical covariates, and the median OR (MOR) used to describe the relative impact of the surgeon and institution. RESULTS: Six thousand five hundred ninety-four women (22.4%) underwent mastectomy. Unadjusted rates of mastectomy ranged from 0% in the bottom quintile of surgeons to 58.0% in the top quintile. On multivariable analysis, the individual surgeon (MOR 1.97) had a greater impact on mastectomy than did the institution (MOR 1.71) or all other clinical and demographic variables except tumor size (OR 3.06) and nodal status (OR 2.95). Surgeons with more years in practice, or those with a lower case volume were more likely to perform mastectomy (P < 0.05). CONCLUSION: The individual surgeon influences the likelihood of mastectomy for the treatment of localized breast cancer. Further research should focus on physician-related biases that influence this decision to ensure patient autonomy.

The Impact of Radiation Oncologists on the Early Adoption of Hypofractionated Radiation Therapy for Early-Stage Breast Cancer.

PURPOSE: Despite multiple randomized trials showing the efficacy of hypofractionated radiation therapy in early-stage breast cancer, the United States has been slow to adopt this treatment. The goal of this study was to evaluate the impact of individual radiation oncologists on the early adoption of hypofractionated radiation therapy for early-stage breast cancer. METHODS: We identified 22,233 Medicare beneficiaries with localized breast cancer that was diagnosed from 2004 to 2011 who underwent breast-conserving surgery with adjuvant radiation. Multilevel, multivariable logistic models clustered by radiation oncologist and geographic practice area were used to determine the impact of the provider and geographic region on the likelihood of receiving hypofractionated compared with standard fractionated radiation therapy while controlling for a patient's clinical and demographic covariates. Odds ratios (OR) describe the impact of demographic or clinical covariates, and the median OR (MOR) describes the relative impact of the individual radiation oncologist and geographic region on the likelihood of undergoing hypofractionated radiation therapy. RESULTS: Among the entire cohort, 2333 women (10.4%) were treated with hypofractionated radiation therapy, with unadjusted rates ranging from 0.0% in the bottom quintile of radiation oncologists to 30.4% in the top quintile. Multivariable analysis found that the individual radiation oncologist (MOR 3.08) had a greater impact on the use of hypofractionation than did geographic region (MOR 2.10) or clinical and demographic variables. The impact of the provider increased from the year 2004 to 2005 (MOR 2.82) to the year 2010 to 2011 (MOR 3.16) despite the publication of long-term randomized trial results in early 2010. Male physician and radiation oncologists treating the highest volume of breast cancer patients were less likely to perform hypofractionation (P<.05). CONCLUSIONS: The individual radiation oncologist strongly influenced the likelihood of a patient's receiving hypofractionated radiation therapy, and this trend increased despite the publication of long-term data showing equivalence to standard fractionation. Future research should focus on physician-related factors that influence this decision.

Modern Radiation Therapy and Cardiac Outcomes in Breast Cancer.

PURPOSE: Adjuvant radiation therapy, which has proven benefit against breast cancer, has historically been associated with an increased incidence of ischemic heart disease. Modern techniques have reduced this risk, but a detailed evaluation has not recently been conducted. The present study evaluated the effect of current radiation practices on ischemia-related cardiac events and procedures in a population-based study of older women with nonmetastatic breast cancer. METHODS AND MATERIALS: A total of 29,102 patients diagnosed from 2000 to 2009 were identified from the Surveillance, Epidemiology, and End Results-Medicare database. Medicare claims were used to identify the radiation therapy and cardiac outcomes. Competing risk models were used to assess the effect of radiation on these outcomes. RESULTS: Patients with left-sided breast cancer had a small increase in their risk of percutaneous coronary intervention (PCI) after radiation therapy-the 10-year cumulative incidence for these patients was 5.5% (95% confidence interval [CI] 4.9%-6.2%) and 4.5% (95% CI 4.0%-5.0%) for right-sided patients. This risk was limited to women with previous cardiac disease. For patients who underwent PCI, those with left-sided breast cancer had a significantly increased risk of cardiac mortality with a subdistribution hazard ratio of 2.02 (95% CI 1.23-3.34). No other outcome, including cardiac mortality for the entire cohort, showed a significant relationship with tumor laterality. CONCLUSIONS: For women with a history of cardiac disease, those with left-sided breast cancer who underwent radiation therapy had increased rates of PCI and a survival decrement if treated with PCI. The results of the present study could help cardiologists and radiation oncologists better stratify patients who need more aggressive cardioprotective techniques.

Importance of Radiation Oncologist Experience Among Patients With Head-and-Neck Cancer Treated With Intensity-Modulated Radiation Therapy.

PURPOSE: Over the past decade, intensity-modulated radiation therapy (IMRT) has replaced conventional radiation techniques in the management of head-and-neck cancers (HNCs). We conducted this population-based study to evaluate the influence of radiation oncologist experience on outcomes in patients with HNC treated with IMRT compared with patients with HNC treated with conventional radiation therapy. METHODS: We identified radiation providers from Medicare claims of 6,212 Medicare beneficiaries with HNC treated between 2000 and 2009. We analyzed the impact of provider volume on all-cause mortality, HNC mortality, and toxicity end points after treatment with either conventional radiation therapy or IMRT. All analyses were performed by using either multivariable Cox proportional hazards or Fine-Gray regression models controlling for potential confounding variables. RESULTS: Among patients treated with conventional radiation, we found no significant relationship between provider volume and patient survival or any toxicity end point. Among patients receiving IMRT, those treated by higher-volume radiation oncologists had improved survival compared with those treated by low-volume providers. The risk of all-cause mortality decreased by 21% for every additional five patients treated per provider per year (hazard ratio [HR], 0.79; 95% CI, 0.67 to 0.94). Patients treated with IMRT by higher-volume providers had decreased HNC-specific mortality (subdistribution HR, 0.68; 95% CI, 0.50 to 0.91) and decreased risk of aspiration pneumonia (subdistribution HR, 0.72; 95% CI, 0.52 to 0.99). CONCLUSION: Patients receiving IMRT for HNC had improved outcomes when treated by higher-volume providers. These findings will better inform patients and providers when making decisions about treatment, and emphasize the critical importance of high-quality radiation therapy for optimal treatment of HNC.

Clinical and cosmetic outcomes in patients treated with high-dose-rate electronic brachytherapy for nonmelanoma skin cancer.

PURPOSE: To retrospectively analyze clinical and cosmetic outcomes in patients treated for nonmelanoma skin cancer (NMSC) with high-dose-rate (HDR) electronic brachytherapy (EBT) using surface applicators. METHODS AND MATERIALS: We identified 127 patients who had 154 NMSC lesions, 149 of which were basal cell carcinoma, treated with HDR EBT at our institution between July 2012 and March 2014. Lesions were treated to 40 Gy in 8 fractions. Local control, acute toxicity, late toxicity, and cosmetic outcomes were analyzed retrospectively. Acute and late toxicities were graded using the Common Terminology Criteria for Adverse Events, version 4.0. Cosmetic outcomes were graded using a standard scale based on the Radiation Therapy Oncology Group and European Organization for Research and Treatment of Cancer Late Radiation Morbidity Scoring Schema. RESULTS: Median (range) follow-up from completion of treatment was 16.1 (3.4-34.8 months). The overall crude recurrence rate was 1.3% (n = 2). Grade 0 to 1 acute radiation dermatitis was observed in 52.6% of treated lesions (n = 81), grade 2 in 34.4% (n = 53), and grade 3 in 13.0% (n = 20). No acute toxicity greater than grade 3 was observed and all acute toxic events resolved after treatment. Grade 0 to 1 late toxicity was observed in 94.2% of cases (n = 145), and grade 2 in 5.8% (n = 9). No late toxicity greater than grade 2 was observed. Across the 152 controlled lesions, cosmetic results were excellent in 94.2% of treated lesions (n = 145), good in 3.3% (n = 5), fair in 0.7% (n = 1), and poor in 0.7% (n = 1). CONCLUSIONS: HDR EBT confers promising local control, minimal toxicity, and excellent cosmesis in our institutional experience. It should be considered ideal for NMSC of the head and neck, particularly for basal cell carcinoma involving central facial locations where surgical cosmesis may be inferior.

The impact of radiotherapy costs on clinical outcomes in breast cancer.

BACKGROUND AND PURPOSE: In cost-effective healthcare systems, the cost of services should parallel patient complexity or quality of care. The purpose of this study was to determine whether the cost of radiotherapy correlates with patient-related outcomes among a large cohort of breast cancer patients treated with adjuvant breast radiation. MATERIALS AND METHODS: 23,127 women with non-metastatic breast cancer undergoing radiotherapy after breast conservation surgery were identified from the Surveillance, Epidemiology, and End Results database from 2000 to 2009. Medicare reimbursements were used as a proxy for cost of radiotherapy, and Medicare claims were examined to identify local toxicities, and breast cancer-related endpoints. The impact of cost on these outcomes was studied with multivariable Fine-Gray models to account for competing risks. RESULTS: The median cost (and interquartile range) of a course of breast radiation was $8100 ($6700-9700). Increased radiation costs were not associated with the occurrence of treatment-related toxicities (all p-values>0.05), ipsilateral breast recurrence (p=0.55), or breast cancer-related mortality (p=0.55). CONCLUSION: Higher costs for adjuvant radiation in breast cancer were not associated with a decreased risk of patient-related outcomes suggesting inefficiency in Medicare reimbursements. Future efforts should focus on prospective evaluation of alternative payment models for radiotherapy.

Variation in the Cost of Radiation Therapy Among Medicare Patients With Cancer.

PURPOSE: Radiation therapy represents a major source of health care expenditure for patients with cancer. Understanding the sources of variability in the cost of radiation therapy is critical to evaluating the efficiency of the current reimbursement system and could shape future policy reform. This study defines the magnitude and sources of variation in the cost of radiation therapy for a large cohort of Medicare beneficiaries. PATIENTS AND METHODS: We identified 55,288 patients within the SEER database diagnosed with breast, lung, or prostate cancer between 2004 and 2009. The cost of radiation therapy was estimated from Medicare reimbursements. Multivariable linear regression models were used to assess the influence of patient, tumor, and radiation therapy provider characteristics on variation in cost of radiation therapy. RESULTS: For breast, lung, and prostate cancers, the median cost (interquartile range) of a course of radiation therapy was $8,600 ($7,300 to $10,300), $9,000 ($7,500 to $11,100), and $18,000 ($11,300 to $25,500), respectively. For all three cancer subtypes, patient- or tumor-related factors accounted for < 3% of the variation in cost. Factors unrelated to the patient, including practice type, geography, and individual radiation therapy provider, accounted for a substantial proportion of the variation in cost, ranging from 44% with breast, 43% with lung, and 61% with prostate cancer. CONCLUSION: In this study, factors unrelated to the individual patient accounted for the majority of variation in the cost of radiation therapy, suggesting potential inefficiency in health care expenditure. Future research should determine whether this variability translates into improved patient outcomes for further evaluation of current reimbursement practices.

Postoperative stereotactic radiosurgery without whole-brain radiation therapy for brain metastases: potential role of preoperative tumor size.

PURPOSE: Radiation therapy following resection of a brain metastasis increases the probability of disease control at the surgical site. We analyzed our experience with postoperative stereotactic radiosurgery (SRS) as an alternative to whole-brain radiotherapy (WBRT), with an emphasis on identifying factors that might predict intracranial disease control and overall survival (OS). METHODS AND MATERIALS: We retrospectively reviewed all patients through December 2008, who, after surgical resection, underwent SRS to the tumor bed, deferring WBRT. Multiple factors were analyzed for time to intracranial recurrence (ICR), whether local recurrence (LR) at the surgical bed or "distant" recurrence (DR) in the brain, for time to WBRT, and for OS. RESULTS: A total of 49 lesions in 47 patients were treated with postoperative SRS. With median follow-up of 9.3 months (range, 1.1-61.4 months), local control rates at the resection cavity were 85.5% at 1 year and 66.9% at 2 years. OS rates at 1 and 2 years were 52.5% and 31.7%, respectively. On univariate analysis (preoperative) tumors larger than 3.0 cm exhibited a significantly shorter time to LR. At a cutoff of 2.0 cm, larger tumors resulted in significantly shorter times not only for LR but also for DR, ICR, and salvage WBRT. While multivariate Cox regressions showed preoperative size to be significant for times to DR, ICR, and WBRT, in similar multivariate analysis for OS, only the graded prognostic assessment proved to be significant. However, the number of intracranial metastases at presentation was not significantly associated with OS nor with other outcome variables. CONCLUSIONS: Larger tumor size was associated with shorter time to recurrence and with shorter time to salvage WBRT; however, larger tumors were not associated with decrements in OS, suggesting successful salvage. SRS to the tumor bed without WBRT is an effective treatment for resected brain metastases, achieving local control particularly for tumors up to 3.0 cm diameter.

Stereotactic radiosurgery to the resection cavity of brain metastases: a retrospective analysis and literature review.

PURPOSE: The aim of this study was to analyze results of stereotactic radiosurgery (SRS) as adjuvant therapy for resected brain metastases. METHODS: Medical records of patients treated at a single institution with SRS to the postoperative cavity of brain metastases were retrospectively reviewed. Patients who completed the prescribed SRS regimen following gross-total resection and had no previous whole brain radiotherapy were included in the study. Kaplan-Meier analyses were used to estimate local (LC) and intracranial control (IC), and overall survival (OS) rates. RESULTS: Between April 2005 and July 2010, 77 patients (median age 63 years) with 89 metastases met the inclusion criteria. The median prescription dose was 18 Gy (12-27 Gy) delivered in 1-3 fractions for a median target volume of 7.6 cm(3) (0.5-59 cm(3)). The 6-month, 1-year, and 2-year LC rates were 76.1, 76.1, and 74.3%, respectively. The 6-month, 1-year, and 2-year IC rates were 75.2, 54, and 43.6%, respectively. With a median follow-up of 13.8 months, the median OS was 14.5 months (1.9-51.4 months) after SRS. The overall 6-month, 1-year, and 2-year OS rates were 91, 62.5, and 43.6%, respectively. Complications included 2 patients with radiation necrosis. CONCLUSION: Adjuvant radiosurgery to the tumor cavity of resected brain metastases is well-tolerated and achieves LC in the majority of patients.

Adverse events in the long-term follow-up of patients treated with samarium Sm 153 lexidronam for osseous metastases.

PURPOSE: To investigate adverse events after samarium Sm 153 lexidronam and the effect of pre- and post-samarium Sm 153 lexidronam external beam radiation therapy (EBRT) and/or chemotherapy on myelosuppression in patients who received samarium Sm 153 lexidronam for osseous metastases. METHODS AND MATERIALS: We performed a single-institution retrospective review of 139 patients treated with samarium Sm 153 lexidronam between November 1997 and February 2008. New-onset adverse events after samarium Sm 153 lexidronam were reported. The effect of samarium Sm 153 lexidronam on platelet and peripheral white blood cell counts and the duration of myelosuppression after samarium Sm 153 lexidronam plus EBRT and/or chemotherapy were calculated. Differences in the prevalence of adverse events among patients with varying treatment histories were evaluated with the Pearson chi-square test. RESULTS: Hematologic follow-up was available for 103 patients. Chemotherapy and/or EBRT had no effect on the magnitude or duration of myelosuppression. The most common nonhematologic adverse events were acute lower extremity edema (n = 27) and acute and transient neuropathy (n = 29). Patients treated with chemotherapy after samarium Sm 153 lexidronam had a higher prevalence of lower extremity edema (9 of 18 [50%]) than those who were not treated with chemotherapy after samarium Sm 153 lexidronam (18 of 85 [21.2%]) (p = 0.01, chi-square test). No adverse events were correlated with EBRT. CONCLUSIONS: Our observation of new-onset, acute and transient edema and neuropathy after samarium Sm 153 lexidronam and of a relationship between edema and post-samarium Sm 153 lexidronam chemotherapy suggests the need for re-examination of patients in past series or for a prospective investigation with nonhematologic adverse events as a primary endpoint.

Radiotherapy and temozolomide for newly diagnosed glioblastoma and anaplastic astrocytoma: validation of Radiation Therapy Oncology Group-Recursive Partitioning Analysis in the IMRT and temozolomide era.

Since the development of the Radiation Therapy Oncology Group-Recursive Partitioning Analysis (RTOG-RPA) risk classes for high-grade glioma, radiation therapy in combination with temozolomide (TMZ) has become standard care. While this combination has improved survival, the prognosis remains poor in the majority of patients. Therefore, strong interest in high-grade gliomas from basic research to clinical trials persists. We sought to evaluate whether the current RTOG-RPA retains prognostic significance in the TMZ era or alternatively, if modifications better prognosticate the optimal selection of patients with similar baseline prognosis for future clinical protocols. The records of 159 patients with newly-diagnosed glioblastoma (GBM, WHO grade IV) or anaplastic astrocytoma (AA, WHO grade III) were reviewed. Patients were treated with intensity-modulated radiation therapy (IMRT) and concurrent followed by adjuvant TMZ (n = 154) or adjuvant TMZ only (n = 5). The primary endpoint was overall survival. Three separate analyses were performed: (1) application of RTOG-RPA to the study cohort and calculation of subsequent survival curves, (2) fit a new tree model with the same predictors in RTOG-RPA, and (3) fit a new tree model with an expanded predictor set. All analyses used a regression tree analysis with a survival outcome fit to formulate new risk classes. Overall median survival was 14.9 months. Using the RTOG-RPA, the six classes retained their relative prognostic significance and overall ordering, with the corresponding survival distributions significantly different from each other (P < 0.01, χ(2) statistic = 70). New recursive partitioning limited to the predictors in RTOG-RPA defined four risk groups based on Karnofsky Performance Status (KPS), histology, age, length of neurologic symptoms, and mental status. Analysis across the expanded predictors defined six risk classes, including the same five variables plus tumor location, tobacco use, and hospitalization during radiation therapy. Patients with excellent functional status, AA, and frontal lobe tumors had the best prognosis. For patients with newly-diagnosed high-grade gliomas, RTOG-RPA classes retained prognostic significance in patients treated with TMZ and IMRT. In contrast to RTOG-RPA, in our modified RPA model, KPS rather than age represented the initial split. New recursive partitioning identified potential modifications to RTOG-RPA that should be further explored with a larger data set.

Combined endoscopic endonasal surgery and fractionated stereotactic radiosurgery (fSRS) for complex cranial base tumors-early clinical outcomes.

Endoscopic endonasal surgery (EES) has been shown to be a feasible approach to cranial base tumors while reducing post-operative morbidity. Using the endoscopic endonasal approach alone or in combination with open approaches may provide advantages over conventional approaches. However, the balance between maximal resection and minimal injury to neurovascular structures frequently precludes gross total resection (GTR). Consequently, adjuvant radiation therapy may be an important option to improve local control (LC) of residual disease. In this retrospective series, we report clinical outcomes, morbidity, and LC of 40 patients with cranial base tumors treated with EES +/- combined open approach followed by fSRS (CyberKnife, Accuray Inc.). 26 patients had benign disease, 7 had newly diagnosed malignant disease, and 7 had previously resected malignant disease. Surgical outcomes were evaluable in all patients. LC after fSRS was evaluable in 39 patients and defined as no evidence of regrowth by MRI, CT, & physical examination. GTR was achieved in 12/40. Median post-operative length of stay (LOS) was 3 days. In multivariable analysis controlling for anatomic location and malignant histology, post-operative complications (n = 10) were significantly associated with patients having combined open and EES (p < 0.01, OR = 16.9). SRS was delivered in 1-5 sessions to a median marginal dose of 24.9 Gy. Median follow-up was 24.7 months (range, 1.5 to 61 months). LC was achieved in 89.7% (35/39) of evaluable patients. LC was achieved in 11/12 patients who had GTR. Median progression-free survival was 19.7 months (21.0 months for benign tumors (n = 26), 5.8 months for previously resected malignant disease (n = 7), and 21.2 months for newly diagnosed malignant disease (n = 7). Of the 31 patients who had symptomatic disease at presentation, 18 (58%) reported complete symptom resolution, 9 partial, and 4 no improvement. One patient who received two prior courses of radiation therapy developed osteosclerosis (grade III). Other adverse events were erythema (grade I, n = 5), nausea (grade II, n = 2), conjunctivitis (grade II, n = 1). EES followed by fSRS is a safe and effective management strategy for selected cranial base tumors. EES combined with an open surgical approach may result in increased complications. However, initial follow-up offers encouraging results indicating shorter time to recovery, acceptable LC rates compared to conventional approaches, and similar median time to progression for benign and newly diagnosed malignant disease.