Faculty Bibliography

Purpose/Objective: High-grade glioma is the most common primary malignant tumor of the CNS, with death often resulting from uncontrollable intracranial disease. Radiation dose may be limited by the tolerance of critical structures, such as the brainstem and optic apparatus. In this report, long-term outcomes in patients treated with conventionally fractionated stereotactic boost for tumors in close proximity to critical structures are presented. Materials/Methods: Patients eligible for inclusion in this single institution retrospective review had a pathologically confirmed high-grade glioma status post-surgical resection. Inclusion criteria required tumor location within one centimeter of a critical structure, including the optic chiasm, optic nerve, and brainstem. Radiation therapy consisted of external beam radiation followed by a conventionally fractionated stereotactic boost. Oncologic outcomes and toxicity were assessed. Results: Thirty patients eligible for study inclusion underwent resection of a high-grade glioma. The median initial adjuvant EBRT dose was 50 Gy with a median conventionally fractionated stereotactic boost of 10 Gy. All stereotactic treatments were given in 2 Gy daily fractions. Median follow-up time for the entire cohort was 38 months with a median overall survival of 45 months and 5-year overall survival of 32.5%. The median freedom from local progression was 45 months, and the 5-year freedom from local progression was 29.7%. Two cases of radiation retinopathy were identified following treatment. No patient experienced toxicity attributable to the optic chiasm, optic nerve, or brainstem and no grade 3+ radionecrosis was observed. Conclusions: Oncologic and toxicity outcomes in high-grade glioma patients with tumors in unfavorable locations treated with conventionally fractionated stereotactic boost are comparable to those reported in the literature. This treatment strategy is appropriate for those patients with resected high-grade glioma in close proximity to critical structures.

BACKGROUND:Brain metastases of gastrointestinal origin are a rare occurrence. Radiation therapy (RT) in the form of stereotactic radiosurgery (SRS) or whole brain radiation therapy (WBRT) is an effective established treatment modality in either the definitive or adjuvant setting. The aim of this study is to assess the long-term clinical outcomes of patients with gastrointestinal (GI) brain metastases treated with SRS or WBRT. METHODS:In this single institutional retrospective review, we detail the outcomes of patients diagnosed with metastatic brain tumors from an adenocarcinoma gastrointestinal primary. Patients were treated using stereotactic radiosurgery or whole brain radiation therapy. Initial site control (defined as lesions visualized on imaging at time of treatment), new site control (defined as new intracranial lesions visualized on follow-up imaging), and overall survival were calculated using the Kaplan-Meier method. RESULTS:Thirty-three patients were treated from August 2008 to December 2015. Primary malignancy locations were as follows: 18 colon, 6 esophagus, 4 rectum, 5 other. Median total dose delivered was 25 Gy (18-35 Gy) in a median of 4 fractions for SRS and 30 Gy (10.8-40 Gy) in 10 fractions for WBRT. Crude initial site control at last radiographic follow-up was 64.3% after SRS and 41.7% after WBRT. Eleven of the 28 brain lesions (39.3%) treated with SRS had resection of the SRS-treated lesion prior to radiation therapy. Five of the twelve patients (41.7%) undergoing WBRT underwent cranial resection prior to radiation therapy. Crude new site control at last radiographic follow-up was 46.4% after SRS and 83.3% after WBRT. Kaplan-Meier analysis of overall survival did not show any statistically significant difference between WBRT and SRS (p = 0.424). Median overall survival for SRS patients was 5.2 months (0.5-57.5) and for WBRT patients 4.4 months (0-15). Kaplan-Meier analysis of new site control was significantly improved with WBRT versus SRS (p = 0.017). Total dose, treatment with WBRT, and active extracranial disease were statistically significant on multivariate analysis for new site control (p < 0.05). CONCLUSIONS:Survival and intracranial disease control are poor following RT for brain metastases from GI primaries. In this small series, outcomes are worse than published series for other primary malignancies metastatic to the brain and further research into methods of local control improvement is warranted. Future studies should explore the utility of dose escalation or radiosensitization in this patient population.

Hepatobiliary malignancies represent a heterogeneous group of diseases, which often arise in a background of underlying hepatic dysfunction complicating their local management. Surgical resection continues to be the standard of care for hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC); unfortunately the majority of patients are inoperable at presentation. The aggressiveness of these lesions makes locoregional control of particular importance. Historical experience with less sophisticated radiotherapy resulted in underwhelming efficacy and oftentimes prohibitive liver toxicity. However, with the advent of extremely conformal and precise radiotherapy delivery, dose escalation to the tumor with sparing of surrounding normal tissue has yielded notable improvements in efficacy for this modality of treatment. Dose escalation has come in a variety of forms most notably as stereotactic body radiation therapy (SBRT) and hypofractionated proton therapy. As radiation techniques continue to improve, their proper incorporation into the local management of hepatobiliary malignancies will be paramount in improving the prognosis of what is a grave diagnosis.

PURPOSE/OBJECTIVE/OBJECTIVE:Local treatment options for patients with in-field non-small cell lung cancer (NSCLC) recurrence following conventionally fractionated external beam radiation therapy (CF-EBRT) are limited. Stereotactic body radiation therapy (SBRT) is a promising modality to achieve reasonable local control, although toxicity remains a concern. MATERIALS/METHODS/METHODS:Patients previously treated with high-dose CF-EBRT (≥59.4 Gy, ≤3 Gy/fraction) for non-metastatic NSCLC who underwent salvage SBRT for localized ultra-central in-field recurrence were included in this analysis. Ultra-central recurrences were defined as those abutting the trachea, mainstem bronchus, or esophagus and included both parenchymal and nodal recurrences. The Kaplan-Meier method was used to estimate local control and overall survival. Durable local control was defined as ≥12 months. Toxicity was scored per the CTC-AE v4.0. RESULTS:Twenty patients were treated with five-fraction robotic SBRT for ultra-central in-field recurrence following CF-EBRT. Fifty percent of recurrences were adenocarcinoma, while 35% of tumors were classified as squamous cell carcinoma. The median interval between the end of CF-EBRT and SBRT was 23.3 months (range: 2.6 - 93.6 months). The median CF-EBRT dose was 63 Gy (range: 59.4 - 75 Gy), the median SBRT dose was 35 Gy (range: 25 - 45 Gy), and the median total equivalent dose in 2 Gy fractions (EQD2) was 116 Gy (range: 91.3 - 136.7 Gy). At a median follow-up of 12 months for all patients and 37.5 months in surviving patients, the majority of patients (90%) have died. High-dose SBRT was associated with improved local control (p < .01), and the one-year overall survival and local control were 77.8% and 66.7% respectively in this sub-group. No late esophageal toxicity was noted, although a patient who received an SBRT dose of 45 Gy (total EQD2: 129.7 Gy) experienced grade 5 hemoptysis 35 months following treatment. CONCLUSIONS:Although the overall prognosis for patients with in-field ultra-central NSCLC recurrences following CF-EBRT remains grim, five-fraction SBRT was well tolerated with an acceptable toxicity profile. Dose escalation above 35 Gy may offer improved local control, however caution is warranted when treating high-risk recurrences with aggressive regimens.

Stereotactic body radiation therapy (SBRT) has become a viable treatment option for the many patients who receive a diagnosis of localized prostate cancer each year. Technological advancements have led to tight target conformality, allowing for high-dose-per-fraction delivery without untoward normal tissue toxicity. Biochemical control, now reported up to 5 years, appears to compare favorably with dose-escalated conventionally fractionated radiotherapy. Moreover, toxicity and quality of life follow-up data indicate genitourinary and gastrointestinal toxicities are likewise comparable to conventional radiation therapy. Nevertheless, because of the long natural history of prostate cancer, extended follow-up will be necessary to confirm these impressive initial results. Within this prostate SBRT review, we explore the detailed rationale for SBRT treatment, the diverse SBRT techniques utilized and their unique technical considerations, and finally data for SBRT clinical efficacy and treatment-related toxicity.

PURPOSE/OBJECTIVE:Respiratory-induced tumor motion of upper gastrointestinal (GI) tumors during radiation therapy is often assessed using a single 4-dimensional computed tomography (4D-CT) and presumed to be representative during fractionated treatment regimens. The purpose of this study was to examine the intra- and interfraction correlations of tumor motion between pretreatment 4D-CT and real-time fiducial-based motion tracking in patients treated with fractionated stereotactic body radiation therapy (SBRT) for upper GI malignancies. METHODS AND MATERIALS/METHODS:Fourteen patients with upper GI tumors underwent fractionated SBRT using the CyberKnife radiosurgical system with Synchrony respiratory motion management. Before treatment, each patient underwent a free-breathing 4D-CT scan and fiducial motion was tracked for each phase of the respiratory cycle. Real-time fiducial positions recorded during delivery of each SBRT fraction were extracted from the CyberKnife planning system. Displacements were compared between those predicted by 4D-CT and those recorded by Synchrony during treatment in the left-right (LR), anteroposterior (AP), and superoinferior (SI) directions. RESULTS:The 4D-CT scans demonstrated little correlation with real-time mean fiducial displacement as determined by Pearson correlation with coefficients of 0.45, 0.52, and 0.63 in the SI, AP, and LR directions, respectively. Cohort-averaged maximum fiducial displacements based on 4D-CT and real-time tracking were measured to be 3.86 ± 1.40 mm versus 10.73 ± 7.03 mm, 2.29 ± 1.02 mm versus 4.44 ± 3.33 mm, and 1.45 ± 0.49 mm versus 2.67 ± 2.49 mm in the SI, AP, and LR directions, respectively. Mean fiducial displacements were greater than that predicted by the maximum displacements on the corresponding 4D-CT scan in 39%, 22%, and 25% of SBRT fractions in the SI, AP, and LR directions, respectively. CONCLUSIONS:Comparison of 4D-CT with real-time fiducial tracking demonstrated significant inter- and intrafractional discrepancies, particularly in the SI direction, which could result in compromise of target coverage when planning with a single free-breathing 4D-CT.