Intensity-Modulated Radiation Therapy with Stereotactic Body Radiation Therapy Boost for Unfavorable Prostate Cancer: The Georgetown University Experience.

PURPOSE/OBJECTIVES: Stereotactic body radiation therapy (SBRT) is emerging as a minimally invasive alternative to brachytherapy to deliver highly conformal, dose--escalated radiation therapy (RT) to the prostate. SBRT alone may not adequately cover the tumor extensions outside the prostate commonly seen in unfavorable prostate cancer. External beam radiation therapy (EBRT) with high dose rate brachytherapy boost is a proven effective therapy for unfavorable prostate cancer. This study reports on early prostate-specific antigen and prostate cancer-specific quality of life (QOL) outcomes in a cohort of unfavorable patients treated with intensity-modulated radiation therapy (IMRT) and SBRT boost. MATERIALS/METHODS: Prostate cancer patients treated with SBRT (19.5 Gy in three fractions) followed by fiducial-guided IMRT (45-50.4 Gy) from March 2008 to September 2012 were included in this retrospective review of prospectively collected data. Biochemical failure was assessed using the Phoenix definition. Patients completed the expanded prostate cancer index composite (EPIC)-26 at baseline, 1 month after the completion of RT, every 3 months for the first year, then every 6 months for a minimum of 2 years. RESULTS: One hundred eight patients (4 low-, 45 intermediate-, and 59 high-risk) with median age of 74 years completed treatment, with median follow-up of 4.4 years. Sixty-four percent of the patients received androgen deprivation therapy prior to the initiation of RT. The 3-year actuarial biochemical control rates were 100 and 89.8% for intermediate- and high-risk patients, respectively. At the initiation of RT, 9 and 5% of men felt their urinary and bowel function was a moderate to big problem, respectively. Mean EPIC urinary and bowel function and bother scores exhibited transient declines, with subsequent return to near baseline. At 2 years posttreatment, 13.7 and 5% of men felt their urinary and bowel function was a moderate to big problem, respectively. CONCLUSION: At 3-year follow-up, biochemical control was favorable. Acute urinary and bowel symptoms were comparable to conventionally fractionated IMRT and brachytherapy. Patients recovered to near their baseline urinary and bowel function by 2 years posttreatment. A combination of IMRT with SBRT boost is well tolerated with minimal impact on prostate cancer-specific QOL.

Safety and efficacy of hypofractionated stereotactic body reirradiation in head and neck cancer: Long-term follow-up of a large series.

BACKGROUND: The purpose of this study was to report long-term outcomes for a large cohort of patients with head and neck squamous cell carcinoma (HNSCC) who underwent stereotactic body radiotherapy (SBRT) reirradiation. METHODS: From 2002 to 2011, 85 patients with previously irradiated HNSCC were treated with SBRT to 94 lesions. Some underwent surgery (29%), and many were treated with induction, concurrent, and/or adjuvant chemotherapy or biologic therapy (70%). RESULTS: Reirradiation occurred at a median interval from initial radiotherapy (RT) of 32 months. Median follow-up for survivors was 17.3 months. Two-year Kaplan-Meier estimates of overall survival (OS) and locoregional control for patients and lesions treated with curative intent were 24% and 28%, respectively. Interval from initial RT to SBRT of 2 years or more was associated with improved OS (p = .019). Five patients had grade 3 or higher late toxicity (5.9%). CONCLUSION: SBRT reirradiation results in limited toxicity. Further research is needed to refine optimal roles for SBRT and intensity-modulated radiotherapy (IMRT) reirradiation.

Radiation therapy at the end of life: a population-based study examining palliative treatment intensity.

BACKGROUND: To examine factors associated with the use of radiation therapy (RT) at the end of life in patients with breast, prostate, or colorectal cancer. METHODS: Using data from the Surveillance, Epidemiology, and End Results (SEER) - Medicare database, patients were over age 65 and diagnosed between January 1, 2004 and December 31, 2011 with any stage of cancer when the cause of death, as defined by SEER, was cancer; or with stage 4 cancer, who died of any cause. We employed multiple logistic regression models to identify patient and health systems factors associated with palliative radiation use. RESULTS: 50% of patients received RT in the last 6 months of life. RT was used less frequently in older patients and in non-Hispanic white patients. Similar patterns were observed in the last 14 days of life. Chemotherapy use in the last 6 months of life was strongly correlated with receiving RT in the last 6 months (OR 2.72, 95% CI: 2.59-2.88) and last 14 days of life (OR 1.55, 95% CI: 1.40-1.66). Patients receiving RT accrued more emergency department visits, radiographic exams and physician visits (all comparisons p < 0.0001). CONCLUSIONS: Among patients with breast, colorectal, and prostate cancer, palliative RT use was common. End-of-life RT correlated with end-of-life chemotherapy use, including in the last 14 days of life, when treatment may cause increased treatment burden without improved quality of life. Research is needed optimize the role and timing of RT in palliative care.

Stereotactic radiosurgery for single brain metastases from non-small cell lung cancer: progression of extracranial disease correlates with distant intracranial failure.

BACKGROUND: Limited data exist regarding management of patients with a single brain lesion with extracranial disease due to non-small cell lung cancer (NSCLC). METHODS: Eighty-eight consecutive patients with a single brain lesion from NSCLC in the presence of extracranial disease were treated with stereotactic radiosurgery (SRS) alone. Local control (LC), distant intracranial failure (DIF), overall survival (OS), and toxicity were assessed. The logrank test was used to identify prognostic variables. RESULTS: Median OS was 10.6 months. One-year DIF was 61%; LC 89%. Treatments were delivered in 1-5 fractions to median BED10 = 60 Gy. Five patients developed radionecrosis. Factors associated with shortened OS included poor performance status (PS) (p = 0.0002) and higher Recursive Partitioning Analysis class (p = 0.017). For patients with PS 0, median survival was 22 months. DIF was associated with systemic disease status (progressive vs. stable) (p = 0.0001), as was BED (p = 0.021) on univariate analysis, but only systemic disease (p = 0.0008) on multivariate analysis. CONCLUSIONS: This study identifies a patient population that may have durable intracranial control after treatment with SRS alone. These data support the need for prospective studies to optimize patient selection for up-front SRS and to characterize the impact of DIF on patients' quality of life.

Predicting survival in patients with brain metastases treated with radiosurgery using artificial neural networks.

BACKGROUND: Artificial neural networks (ANNs) excel at analyzing challenging data sets and can be exceptional tools for decision support in clinical environments. The present study pilots the use of ANNs for determining prognosis in neuro-oncology patients. OBJECTIVE: To determine whether ANNs perform better at predicting 1-year survival in a group of patients with brain metastasis compared with traditional predictive tools. METHODS: : ANNs were trained on a multi-institutional data set of radiosurgery patients to predict 1-year survival on the basis of several input factors. A single ANN, an ensemble of 5 ANNs, and logistic regression analyses were compared for efficacy. Sensitivity analysis was used to identify important variables in the ANN model. RESULTS: A total of 196 patients were divided up into training, testing, and validation data sets consisting of 98, 49, and 49 patients, respectively. Patients surviving at 1 year tended to be female (P = .001) and of good performance status (P = .01) and to have favorable primary tumor histology (P = .001). The pooled voting of 5 ANNs performed significantly better than the multivariate logistic regression model (P = .02), with areas under the curve of 84% and 75%, respectively. The ensemble also significantly outperformed 2 commonly used prognostic indexes. Primary tumor subtype and performance status were identified on sensitivity analysis to be the most important variables for the ANN. CONCLUSION: ANNs outperform traditional statistical tools and scoring indexes for predicting individual patient prognosis. Their facile implementation, robustness in the presence of missing data, and ability to continuously learn make them excellent choices for use in complicated clinical environments.

The impact of radiosurgery fractionation and tumor radiobiology on the local control of brain metastases.

OBJECT: Experience with whole-brain radiation therapy for metastatic tumors in the brain has identified a subset of tumors that exhibit decreased local control with fractionated regimens and are thus termed radioresistant. With the advent of frameless radiosurgery, fractionated radiosurgery (2-5 fractions) is being used increasingly for metastatic tumors deemed too large or too close to crucial structures to be treated in a single session. The authors retrospectively reviewed metastatic brain tumors treated at 2 centers to analyze the dependency of local control rates on tumor radiobiology and dose fractionation. METHODS: The medical records of 214 patients from 2 institutions with radiation-naive metastatic tumors in the brain treated with radiosurgery given either as a single dose or in 2-5 fractions were analyzed retrospectively. The authors compared the local control rates of the radiosensitive with the radioresistant tumors after either single-fraction or fractionated radiosurgery. RESULTS: There was no difference in local tumor control rates in patients receiving single-fraction radiosurgery between radioresistant and radiosensitive tumors (p = 0.69). However, after fractionated radiosurgery, treatment for radioresistant tumors failed at a higher rate than for radiosensitive tumors with an OR of 5.37 (95% CI 3.83-6.91, p = 0.032). CONCLUSIONS: Single-fraction radiosurgery is equally effective in the treatment of radioresistant and radiosensitive metastatic tumors in the brain. However, fractionated stereotactic radiosurgery is less effective in radioresistant tumor subtypes. The authors recommend that radioresistant tumors be treated in a single fraction when possible and techniques for facilitating single-fraction treatment or dose escalation be considered for larger radioresistant lesions.

Stereotactic body radiation therapy for liver metastases from colorectal cancer: analysis of safety, feasibility, and early outcomes.

INTRODUCTION: Colorectal cancer (CRC) is the third leading cause of cancer-related death in the U.S. Many patients with CRC develop hepatic metastases as the sole site of metastases. Historical treatment options were limited to resection or conventional radiation therapy. Stereotactic body radiation therapy (SBRT) has emerged as a rational treatment approach. This study reviews our experience with SBRT for patients with liver metastases from CRC. MATERIALS AND METHODS: Fourteen histologically confirmed hepatic CRC metastases in 11 consecutive patients were identified between November, 2004 and June, 2009 at Georgetown University. All patients underwent CT-based treatment planning; a few also had MRI or PET/CT. All patients had fiducial markers placed under CT guidance and were treated using the CyberKnife system. Treatment response and toxicities were examined; survival and local control were evaluated. RESULTS: Most patients were treated to a single hepatic lesion (n = 8), with a few treated to two lesions (n = 3). Median treatment volume was 99.7 cm(3), and lesions were treated to a median BED(10) of 49.7 Gy (range: 28-100.8 Gy). Median follow-up was 21 months; median survival was 16.1 months, with 2 year actuarial survival of 25.7%. One year local control was 72%. Among patients with post-treatment imaging, eight had stable disease (80%) and two had progressive disease (20%) at first follow-up. The most common grade 1-2 acute toxicities included nausea and alterations in liver function tests; there was one grade 3 toxicity (elevated bilirubin), and no grade 4-5 toxicities. DISCUSSION: SBRT is safe and feasible for the treatment of limited hepatic metastases from CRC. Our results compare favorably with outcomes from previous studies of SBRT. Further studies are needed to better define patient eligibility, study the role of combined modality treatment, optimize treatment parameters, and characterize quality of life after treatment.

Physician self-reported treatment of brain metastases according to patients' clinical and demographic factors and physician practice setting.

BACKGROUND: Limited data guide radiotherapy choices for patients with brain metastases. This survey aimed to identify patient, physician, and practice setting variables associated with reported preferences for different treatment techniques. METHOD: 277 members of the American Society for Radiation Oncology (6% of surveyed physicians) completed a survey regarding treatment preferences for 21 hypothetical patients with brain metastases. Treatment choices included combinations of whole brain radiation therapy (WBRT), stereotactic radiosurgery (SRS), and surgery. Vignettes varied histology, extracranial disease status, Karnofsky Performance Status (KPS), presence of neurologic deficits, lesion size and number. Multivariate generalized estimating equation regression models were used to estimate odds ratios. RESULTS: For a hypothetical patient with 3 lesions or 8 lesions, 21% and 91% of physicians, respectively, chose WBRT alone, compared with 1% selecting WBRT alone for a patient with 1 lesion. 51% chose WBRT alone for a patient with active extracranial disease or KPS=50%. 40% chose SRS alone for an 80 year-old patient with 1 lesion, compared to 29% for a 55 year-old patient. Multivariate modeling detailed factors associated with SRS use, including availability of SRS within one's practice (OR 2.22, 95% CI 1.46-3.37). CONCLUSIONS: Poor prognostic factors, such as advanced age, poor performance status, or active extracranial disease, correspond with an increase in physicians' reported preference for using WBRT. When controlling for clinical factors, equipment access was independently associated with choice of SRS. The large variability in preferences suggests that more information about the relative harms and benefits of these options is needed to guide decision-making.

Scoring system predictive of survival for patients undergoing stereotactic body radiation therapy for liver tumors.

BACKGROUND: Stereotactic body radiation therapy (SBRT) is an emerging treatment option for liver tumors. This study evaluated outcomes after SBRT to identify prognostic variables and to develop a novel scoring system predictive of survival. METHODS: The medical records of 52 patients with a total of 85 liver lesions treated with SBRT from 2003 to 2010 were retrospectively reviewed. Twenty-four patients had 1 lesion; 27 had 2 or more. Thirteen lesions were primary tumors; 72 were metastases. Fiducials were placed in all patients prior to SBRT. The median prescribed dose was 30 Gy (range, 16 - 50 Gy) in a median of 3 fractions (range, 1-5). RESULTS: With median follow-up of 11.3 months, median overall survival (OS) was 12.5 months, and 1 year OS was 50.8%. In 42 patients with radiographic follow up, 1 year local control was 74.8%. On univariate analysis, number of lesions (p = 0.0243) and active extralesional disease (p < 0.0001) were predictive of OS; Karnofsky Performance Status (KPS) approached statistical significance (p = 0.0606). A scoring system for predicting survival was developed by allocating 1 point for each of the three following factors: active extralesional disease, 2 or more lesions, and KPS ≤ 80%. Score was associated with OS (p < 0.0001). For scores of 0, 1, 2 and 3, median survival intervals were 34, 12.5, 7.6, and 2.8 months, respectively. CONCLUSIONS: SBRT offers a safe and feasible treatment option for liver tumors. A prognostic scoring system based on the number of liver lesions, activity of extralesional disease, and KPS predicts survival following SBRT and can be used as a guide for prospective validation and ultimately for treatment decision-making.