Faculty Bibliography

PURPOSE/OBJECTIVE:Few definitive treatment options exist for elderly patients diagnosed with early stage breast cancer who are medically inoperable or refuse surgery. Historical data suggest very poor local control with hormone therapy alone. We examined the dosimetric feasibility of hypofractionated radiation therapy using stereotactic ablative radiotherapy (SABR) and proton beam therapy (PBT) as a means of definitive treatment for early stage breast cancer. METHODS AND MATERIALS/METHODS:Fifteen patients with biopsy-proven early stage breast cancer with a clinically visible tumor on preoperative computed tomography scans were identified. Gross tumor volumes were contoured and correlated with known biopsy-proven malignancy on prior imaging. Treatment margins were created on the basis of set-up uncertainty and image guidance capabilities of the three radiation modalities analyzed (3-dimensional conformal radiation therapy [3D-CRT], SABR, and PBT) to deliver a total dose of 50 Gy in 5 fractions. Dose volume histograms were analyzed and compared between treatment techniques. RESULTS: < .0001) between treatment modalities. Overall target coverage of gross tumor and clinical target volumes was excellent with all three modalities. Both SABR and PBT demonstrated significant dosimetric improvements, each in its own unique manner, relative to 3D-CRT. Dose constraints to normal structures including ipsilateral/contralateral breast, bilateral lungs, and heart were all consistently achieved using SABR and PBT. However, skin or chest wall dose constraints were exceeded in some cases for both SABR and PBT plans and was dictated by the anatomic location of the tumor. CONCLUSIONS:Definitive hypofractionated radiation therapy using SABR and PBT appears to be dosimetrically feasible for the treatment of early stage breast cancer. The anatomical location of the tumor relative to the skin and chest wall appears to be the primary limiting dosimetric factor.

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.

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.

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.

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.