Faculty Bibliography

Surgical treatment remains the only curative treatment for gallbladder cancer. However, even after liver resection, locoregional failure seems to be a significant problem. While there is no Level I evidence, multiple studies have shown benefit for adjuvant radiation in high-risk patients. After extensive liver resection, tolerance to conventional chemoradiation may be limited by potential liver toxicity. Stereotactic body radiotherapy has been used safely and effectively in hepatobiliary malignancies. We present a case report, highlighting the potential therapeutic role of adjuvant stereotactic body radiotherapy (SBRT) for gallbladder cancer.

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.

INTRODUCTION/BACKGROUND:Brain metastases (BM) are common in non-small-cell lung cancer (NSCLC). However, the baseline incidence and evolution of BM over time in oncogene-driven NSCLCs are seldom reported. In this study, we evaluated the frequency of BM in patients with epidermal growth factor receptor (EGFR)-mutated or anaplastic lymphoma kinase (ALK)-rearranged NSCLC. METHODS:The presence of BM, clinicopathologic data, and tumor genotype were retrospectively compiled and analyzed from a cohort of 381 patients. RESULTS:We identified 86 EGFR-mutated (90.7% with metastatic disease; 85.9% received an EGFR inhibitor) and 23 ALK-rearranged (91.3% with metastatic disease; 85.7% received an ALK inhibitor) NSCLCs. BM were present in 24.4% of EGFR-mutated and 23.8% of ALK-rearranged NSCLCs at the time of diagnosis of advanced disease. This study did not demonstrate a difference in the cumulative incidence of BM over time between the two cohorts (EGFR/ALK cohort competing risk regression [CRR] coefficient of 0.78 [95% CI 0.44-1.39], p=0.41). In still living patients with advanced EGFR-mutated NSCLC, 34.2% had BM at 1 year, 38.4% at 2 years, 46.7% at 3 years, 48.7% at 4 years, and 52.9% at 5 years. In still living patients with advanced ALK-rearranged NSCLC, 23.8% had BM at 1 year, 45.5% at 2 years, and 58.4% at 3 years. CONCLUSIONS:BM are frequent in advanced EGFR-mutated or ALK-rearranged NSCLCs, with an estimated >45% of patients with CNS involvement by three years of survival with the use of targeted therapies. These data point toward the CNS as an important unmet clinical need in the evolving schema for personalized care in NSCLC.

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.

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.

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. Renal cell carcinoma is a frequent source of brain metastasis. We present our consecutive series of patients treated with Stereotactic Radiosurgery (SRS) and analyse prognostic factors and the interplay of WBRT and surgical resection. Methods. This is a retrospective study of 66 patients with 207 lesions treated with the Cyberknife radiosurgery system in our institution. The patients were followed up with imaging and clinical examination 1 month and 2-3 months thereafter for the brain metastasis. Patient, treatment, and outcomes characteristics were analysed. Results. 51 male (77.3%) and 15 female (22.7%) patients, with a mean age of 58.9 years (range of 31-85 years) and a median Karnofsky Performance Status (KPS) of 90 (range of 60-100), were included in the study. The overall survival was 13.9 months, 21.9 months, and 5.9 months for the patients treated with SRS only, additional surgery, and WBRT, respectively. The actuarial 1-year Local Control rates were 84%, 94%, and 88% for SRS only, for surgery and SRS, and for WBRT and additional SRS, respectively. Conclusions. Stereotactic radiosurgery is a safe and effective treatment option in patients with brain metastases from RCC. In case of a limited number of brain metastases, surgery and SRS might be appropriate.

BACKGROUND:Ipilimumab improves survival in metastatic melanoma patients. This population frequently develops brain metastases, which have been associated with poor survival and are often treated with radiation. Therefore, outcomes following ipilimumab and radiation are of interest, especially given case reports and animal studies suggest combined treatment may generate abscopal responses outside the radiation field. FINDINGS/RESULTS:We reviewed sixteen consecutive melanoma patients who received 1 to 8 courses of radiation, with a sum total of 51, systematically evaluating abscopal responses by following the largest extra-cranial lesion. We also reviewed other series of patients treated with cranial radiation and ipilimumab. Our patients received between 1 and 8 courses of cranial radiation. Four patients received radiation concurrently with ipilimumab. Median survival was 14 months, and 17 months in patients initially treated with SRS. Interestingly, after radiotherapy, there was a 2.8-fold increased likelihood that the rate of extra-cranial index lesion response improved that didn't reach statistical significance (p = 0.07); this was more pronounced when ipilimumab was administered within three months of radiation (p < 0.01). CONCLUSION/CONCLUSIONS:Our experience and review of recently published series suggest ipilimumab and cranial radiation is well tolerated and can result in prolonged survival. Timing of ipilimumab administration in relation to radiation may impact outcomes. Additionally, our results demonstrate a trend for favorable systemic response following radiotherapy worthy of further evaluation in studies powered to detect potential synergies between radiation and immunotherapy.

BACKGROUND:Unresectable intrahepatic and hilar cholangiocarcinomas carry a dismal prognosis. Systemic chemotherapy and conventional external beam radiation and brachytherapy have been used with limited success. We explored the use of stereotactic body radiotherapy (SBRT) for these patients. METHODS:Patients with unresectable intrahepatic or hilar cholangiocarcinoma or those with positive margins were included in this study. Systemic therapy was used at the discretion of the medical oncologist. The Cyberknife(TM) stereotactic body radiotherapy system used to treat these patients. Patients were treated with three daily fractions. Clinical and radiological follow-up were performed every three months. RESULTS:34 patients (16 male and 18 female) with 42 lesions were included in this study. There were 32 unresectable tumors and two patients with resected tumors with positive margins. The median SBRT dose was 30Gy in three fractions. The median follow-up was 38 months (range 8-71 months). The actuarial local control rate was 79%. The median overall survival was 17 months and the median progression free survival was ten months. There were four Grade III toxicities (12%), including duodenal ulceration, cholangitis and liver abscess. CONCLUSIONS:SBRT is an effective and reasonably safe local therapy option for unresectable intrahepatic or hilar cholangiocarcinoma.

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.