Faculty Bibliography

BACKGROUND:Surgical resection and stereotactic radiosurgery (SRS) are well-established treatment methods for patients with brain metastases, yet their respective roles in the management of brain metastases remain incompletely defined. METHODS:To report on the role of SRS in the treatment of patients with brain metastases from malignant melanoma, a retrospective analysis of 381 intracranial melanoma metastases in 103 consecutive patients who underwent SRS between 2005 and 2011 at Beth Israel Deaconess Medical Center was conducted. The Cyberknife(®) SRS system was used to treat all patients. Clinical, technical, and radiographic data were recorded at presentation and on follow-up. RESULTS:The patient cohort consisted of 40 female (39%) and 63 male (61%) patients with a median age of 57 years. The median overall survival from the time of radiosurgery for the entire patient cohort was 7.6 months. The local control rate at 1-year was 72% for the patients who received surgery followed by SRS and 55% for the entire patient population. Surgery followed by SRS was associated with significantly improved overall survival compared with SRS alone or whole-brain radiation therapy followed by salvage SRS (P < 0.0057). CONCLUSIONS:Both surgery plus SRS and SRS provide comparable local control. Despite the difference in lesion size in the subgroups who received surgery plus SRS and radiosurgery alone, similar outcomes were achieved in both groups, suggesting that surgical treatment of larger lesions can yield results that are not significantly different from small lesions treated by SRS alone.

Purpose. To study radiological response to stereotactic radiotherapy for focal liver tumors. Materials and Methods. In this IRB-approved, HIPAA-compliant study CTs of 68 consecutive patients who underwent stereotactic radiotherapy for liver tumors between 01/2006 and 01/2010 were retrospectively reviewed. Two independent reviewers evaluated lesion volume and enhancement pattern of the lesion and of juxtaposed liver parenchyma. Results. 36 subjects with hepatocellular carcinoma (HCC), 25 with liver metastases, and seven with cholangiocarcinoma (CCC) were included in study. Mean follow-up time was 5.6 ± 7.1 months for HCC, 6.4 ± 5.1 months for metastases, and 10.1 ± 4.8 months for the CCC. Complete response was seen in 4/36 (11.1%) HCCs and 1/25 (4%) metastases. Partial response (>30% decrease in long diameter) was seen in 25/36 (69%) HCCs, 14/25 (58%) metastases, and 7/7 (100%) of CCCs. Partial response followed by local recurrence (>20% increase in long diameter from nadir) occurred in 2/36 (6%) HCCs and 4/25 (17%) metastases. Liver parenchyma adjacent to the lesion demonstrated a prominent halo of delayed enhancement in 27/36 (78%) of HCCs, 19/21 (91%) of metastases, and 7/7 (100%) of CCCs. Conclusion. Sustainable radiological partial response to stereotactic radiotherapy is most frequent outcome seen in liver lesions. Prominent halo of delayed enhancement of the adjacent liver is frequent finding.

BACKGROUND:The purpose of this study was to evaluate treatment patterns and outcomes of stereotactic body radiotherapy (SBRT) for centrally located primary non-small cell lung cancer (NSCLC) or lung metastases from the RSSearch(®) Patient Registry, an international, multi-center patient registry dedicated to radiosurgery and SBRT. METHODS:Eligible patients included those with centrally located lung tumors clinically staged T1-T2 N0, M0, biopsy-confirmed NSCLC or lung metastases treated with SBRT between November 2004 and January 2014. Descriptive analysis was used to report patient demographics and treatment patterns. Overall survival (OS) and local control (LC) were determined using Kaplan-Meier method. Toxicity was reported using the Common Terminology Criteria for Adverse Events version 3.0. RESULTS:In total, 111 patients with 114 centrally located lung tumors (48 T1-T2,N0,M0 NSCLC and 66 lung metastases) were treated with SBRT at 19 academic and community-based radiotherapy centers in the US and Germany. Median follow-up was 17 months (range, 1-72). Median age was 74 years for primary NSCLC patients and 65 years for lung metastases patients (p < 0.001). SBRT dose varied from 16 - 60 Gy (median 48 Gy) delivered in 1-5 fractions (median 4 fractions). Median dose to centrally located primary NSCLC was 48 Gy compared to 37.5 Gy for lung metastases (p = 0.0001) and median BED10 was 105.6 Gy for primary NSCLC and 93.6 Gy for lung metastases (p = 0.0005). Two-year OS for T1N0M0 and T2N0M0 NSCLC was 79 and 32.1 %, respectively (p = 0.009) and 2-year OS for lung metastases was 49.6 %. Two-year LC was 76.4 and 69.8 % for primary NSCLC and lung metastases, respectively. Toxicity was low with no Grade 3 or higher acute or late toxicities. CONCLUSION/CONCLUSIONS:Overall, patients with centrally located primary NSCLC were older and received higher doses of SBRT than those with lung metastases. Despite these differences, LC and OS was favorable for patients with central lung tumors treated with SBRT. Reported toxicity was low, although low grade toxicities were observed in patients where dose tolerances approached or exceeded published guidelines. Prospective studies are needed to further define the optimal SBRT dose for this cohort of patients. TRIAL REGISTRATION/BACKGROUND:Clinicaltrials.gov Identifier: NCT01885299.

OBJECTIVES/OBJECTIVE:Stereotactic body radiotherapy (SBRT) is a definitive local treatment option for patients with stage I non-small cell lung cancer (NSCLC) who are not surgical candidates and patients who refuse surgery. The purpose of this study was to assess the impact of SBRT on T1-T2 NSCLC from a national registry, reflecting practices and outcomes in a real-world setting. METHODS:The RSSearch® Patient Registry was screened for T1-T2N0M0 NSCLC patients treated from May 2004 to May 2013 with SBRT. Descriptive analyses were used for patient, tumor, and treatment characteristics. Overall survival (OS) and local control (LC) were calculated using the Kaplan-Meier method. RESULTS: = 0.062). CONCLUSION/CONCLUSIONS: > 105 Gy.

BACKGROUND AND OBJECTIVES/OBJECTIVE:When surgery is not adequate or feasible, stereotactic body radiotherapy (SBRT) reirradiation has been used for recurrent cancers. We report the outcomes of a series of patients with pelvic recurrences from colorectal cancer reirradiated with SBRT. METHODS:The Cyberknife(TM) Robotic Stereotactic Radiosurgery system with fiducial based real time tracking was used. Patients were followed with imaging of the pelvis. RESULTS:Four women and 14 men with 22 lesions were included. The mean dose was 25 Gy in median of five fractions. The mean prescription isodose was 77%, with a median maximum dose of 32.87 Gy. There were two local failures, with a crude local control rate of 89%. The median overall survival was 43 months. One patient had small bowel perforation and required surgery (Grade IV), two patients had symptomatic neuropathy (1 Grade III) and one patient developed hydronephrosis from ureteric fibrosis requiring a stent (Grade III). CONCLUSIONS:Local recurrence in the pelvis after modern combined modality treatment for colorectal cancer is rare. However it presents a therapeutic dilemma when it occurs; often symptomatic and eventually life threatening. SBRT can be a useful non-surgical modality to control pelvic recurrences after prior radiation for colorectal cancer.

The SRS/SBRT Scientific Meeting 2014, Minneapolis, MN, USA, 7-10 May 2014. The Radiosurgery Society(®), a professional medical society dedicated to advancing the field of stereotactic radiosurgery (SRS) and stereotactic body radiotherapy (SBRT), held the international Radiosurgery Society Scientific Meeting, from 7-10 May 2014 in Minneapolis (MN, USA). This year's conference attracted over 400 attendants from around the world and featured over 100 presentations (46 oral) describing the role of SRS/SBRT for the treatment of intracranial and extracranial malignant and nonmalignant lesions. This article summarizes the meeting highlights for SRS/SBRT treatments, both intracranial and extracranial, in a concise review.

BACKGROUND:Brain metastases are common in patients with melanoma, and optimal management is not well defined. As melanoma has traditionally been thought of as "radioresistant," the role of whole brain radiation therapy (WBRT) in particular is unclear. We conducted this retrospective study to identify prognostic factors for patients treated with stereotactic radiosurgery (SRS) for melanoma brain metastases and to investigate the role of additional up-front treatment with whole brain radiation therapy (WBRT). METHODS:We reviewed records of 147 patients who received SRS as part of initial management of their melanoma brain metastases from January 2000 through June 2010. Overall survival (OS) and time to distant intracranial progression were calculated using the Kaplan-Meier method. Prognostic factors were evaluated using the Cox proportional hazards model. RESULTS:WBRT was employed with SRS in 27% of patients and as salvage in an additional 22%. Age at SRS > 60 years (hazard ratio [HR] 0.64, p = 0.05), multiple brain metastases (HR 1.90, p = 0.008), and omission of up-front WBRT (HR 2.24, p = 0.005) were associated with distant intracranial progression on multivariate analysis. Extensive extracranial metastases (HR 1.86, p = 0.0006), Karnofsky Performance Status (KPS) ≤ 80% (HR 1.58, p = 0.01), and multiple brain metastases (HR 1.40, p = 0.06) were associated with worse OS on univariate analysis. Extensive extracranial metastases (HR 1.78, p = 0.001) and KPS (HR 1.52, p = 0.02) remained significantly associated with OS on multivariate analysis. In patients with absent or stable extracranial disease, multiple brain metastases were associated with worse OS (multivariate HR 5.89, p = 0.004), and there was a trend toward an association with worse OS when up-front WBRT was omitted (multivariate HR 2.56, p = 0.08). CONCLUSIONS:Multiple brain metastases and omission of up-front WBRT (particularly in combination) are associated with distant intracranial progression. Improvement in intracranial disease control may be especially important in the subset of patients with absent or stable extracranial disease, where the competing risk of death from extracranial disease is low. These results are hypothesis generating and require confirmation from ongoing randomized trials.

OBJECTIVE:To determine if concomitant CT-guided biopsy and percutaneous fiducial seed placement in the lung can be performed in a selective patient population without increased complication or decreased success rates compared to either procedure alone. MATERIALS AND METHODS/METHODS:An IRB approved retrospective analysis of 285 consecutive patients that underwent CT-guided placement of fiducial seeds in the lung alone (N=63), with concomitant core biopsy (N=53) or only core biopsy (N=169) was performed. Variables compared included: patient demographics, lesion size, depth from pleura, needle size, number of passes through pleura, number and size of core biopsies, number of seeds placed and technical success rates. Statistical analysis was performed using univariate and multivariate pair-wise comparisons. RESULTS:A pathologic diagnosis of malignancy was confirmed in all cases undergoing seed placement alone and seed placement with concurrent biopsy, and in 144 of the biopsy alone lesions. On univariate analysis, major complication rates were similar for all three groups as were lesion size, depth, number of pleural passes, and technical success. Pair-wise comparisons of the remaining variables demonstrated a significant younger age and smaller needle size in the biopsy only group, and less minor complications in the fiducial only group. Overall there were 80/285 (28.1%) minor and 29/285 (10.2%) major complications. All major complications leading to admission consisted of either pneumothorax or hemothorax, while minor complications included asymptomatic stable or resolving pneumothoraces, transient hemoptysis or small hemothoraces. CONCLUSIONS:A combined procedure of percutaneous pulmonary core biopsy and stereotactic seed placement can be performed without additional risk of a major complication when compared to performing these separately.

OBJECTIVE:Image-guided radiation therapy allows precise tumor targeting using real-time tracking of radiopaque fiducial markers. To enable appropriate tracking, it is recommended to place fiducials with "ideal fiducial geometry" (IFG). Our objectives were to determine the proportion of patients in whom IFG can be achieved when fiducials are placed by endoscopic ultrasound (EUS) and surgery and to determine if attaining IFG is necessary for delivering radiation. METHODS:This single-center retrospective cohort study included 77 patients with biopsy-proven advanced pancreatic cancer who underwent either EUS-guided or laparotomy/laparoscopy-assisted fiducial placement between September 2005 and July 2009. RESULTS:Gold fiducials were implanted by EUS in 39 patients (51%) and by surgery in 38 patients (49%). The proportion of patients with IFG was significantly higher for surgical placement [18/38, 47%; 95% confidence interval (CI), 32%-63%] compared with EUS-guided placement (7/39, 18%; 95% CI, 8%-32%), P = 0.0011. However, fiducial tracking was successfully used for Cyberknife therapy in 35 (90%) of 39 (95% CI, 77%-97%) patients in the EUS group compared with 31 (82%) of 38 (95% CI, 67%-92%) patients in the surgery group. There were 5 procedure-related complications in the EUS group. CONCLUSIONS:Achieving IFG appears unnecessary for successful tracking and delivery of radiation.

BACKGROUND:The RSSearch™ Registry is a multi-institutional, observational, ongoing registry established to standardize data collection from patients treated with stereotactic radiosurgery (SRS) and/or stereotactic body radiotherapy (SBRT). This report describes the design, patient demographics, lesion characteristics, and SRS/SBRT treatment patterns in RSSearch™. Illustrative patient-related outcomes are also presented for two common treatment sites--brain metastases and liver metastases. MATERIALS AND METHODS/METHODS:Thirty-nine US centers participated in RSSearch™. Patients screened for SRS/SBRT were eligible to be enrolled. Descriptive analyses were performed to assess patient characteristics, physician treatment practices, and clinical outcomes. Kaplan-Meier analysis was used to determine overall survival (OS), local progression-free (LPFS), and distant disease-free survival (DDFS). RESULTS:From January, 2008-January, 2013, 11,457 patients were enrolled. The median age was 67 years (range 7-100 years); 51% male and 49% female. Forty-six percent had no prior treatment, 22% had received chemotherapy, 19% radiation therapy and 17% surgery. There were 11,820 lesions from 65 treatment locations; 54% extracranial and 46% intracranial. The most common treatment locations were brain/cranial nerve/spinal cord, lung, prostate and liver. Metastatic lesions accounted for the majority of cases (41.6%), followed by primary malignant (32.9%), benign (10.9%), recurrent (9.4%), and functional diseases (4.3%). SRS/SBRT was used with a curative intent in 39.8% and palliative care in 44.8% of cases. The median dose for all lesions was 30 Gy (range < 1-96.7 Gy) delivered in a median number of 3 fractions. The median dose for lesions in the brain/cranial nerve/spinal cord, lung, liver, pancreas and prostate was 24, 54, 45, 29 and 36.25 Gy, respectively. In a subset analysis of 799 patients with 952 brain metastases, median OS was 8 months. For patients with a Karnofsky performance score (KPS) > 70, OS was 11 months vs. 4 months for KPS ≤ 70. Six-month and 12-month local control was 79% and 61%, respectively for patients with KPS ≤ 70, and 85% and 74%, respectively for patients with KPS > 70. In a second subset analysis including 174 patients with 204 liver metastases, median OS was 22 months. At 1-year, LPFS and DDFS rates were 74% and 53%, respectively. LPFS CONCLUSION/UNASSIGNED:This study demonstrates that collective patterns of care and outcomes research for SRS/SBRT can be performed and reported from data entered by users in a common database. The RSSearch™ dataset represents SRS/SBRT practices in a real world setting, providing a useful resource for expanding knowledge of SRS/SBRT treatment patterns and outcomes and generating robust hypotheses for randomized clinical studies.