Rectal tumor fragmentation as a response pattern following chemoradiation.

Background: Tumor response to neoadjuvant therapy is heterogenous and prognostically important for locally advanced rectal adenocarcinoma (LARC) patients. Commonly applied response classification approaches including tumor regression grading (TRG) and TN downstaging can be discordant. The aim of this study is to compare the prognostic value of discordant tumor response measurement categorized according to the AJCC/CAP TRG schema and ypTN stage. Methods: This is a single-center retrospective review of 90 consecutive patients with stage II-III rectal cancer receiving neoadjuvant chemoradiation (nCRT), total mesorectal excision (TME) and adjuvant chemotherapy (ACT) between 2007 and 2018. Two pathologists re-examined each case to assign a consensus AJCC TRG. A Cox proportional hazards ratio model assessed the effect of patient, tumor, and treatment factors on disease-free survival (DFS). Results: Median follow-up after surgery was 46 months (95% CI: 41-50 months). Median age at diagnosis was 55 years (range: 27-80). Most patients were male (58%) and Caucasian (92%) with clinical stage III disease (68%). Seventy-three patients (81%) underwent low anterior resection (LAR), 17 (19%) underwent abdominoperineal resection (APR). The median interval from completion of nCRT to surgery was 62 days (IQR: 56-70 days). The 4-year OS, DFS, and LC was 92.4%, 74.4%, and 90.2%, respectively. In the multivariate analysis, ypTN downstaging was not prognostically significant; however, AJCC TRG score 3 (minimal tumor response to treatment) was strongly predictive for inferior DFS (3-year DFS 79% vs. 25%, P<0.001). Patients with TRG 3 had a significantly higher risk of both local (75% vs. 5%) and distant failure (75% vs. 19%). Conclusions: Minimal tumor response to neoadjuvant therapy, AJCC TRG 3, irrespective of ypTN downstaging, is a pattern of residual disease that is at highest risk for recurrence. Response categorization discrepancies may be partly explained by alternative patterns of residual disease, including tumor fragmentation, and may be best reflected by TRG. The optimal tumor response categorization method requires further study to best stratify patient risk and management.

Capecitabine and stereotactic radiation in the management of breast cancer brain metastases.

BACKGROUND: Little is known about the safety and efficacy of concurrent capecitabine and stereotactic radiotherapy in the setting of breast cancer brain metastases (BCBM). METHODS: Twenty-three patients with BCBM underwent 31 stereotactic sessions to 90 lesions from 2005 to 2019 with receipt of capecitabine. The Kaplan-Meier method was used to calculate overall survival (OS), local control (LC), and distant intracranial control (DIC) from the date of stereotactic radiation. Imaging was independently reviewed by a neuro-radiologist. RESULTS: Median follow-up from stereotactic radiation was 9.2 months. Receptor types of patients treated included triple negative (n = 7), hormone receptor (HR)+/HER2- (n = 7), HR+/HER2+ (n = 6), and HR-/HER2+ (n = 3). Fourteen patients had stage IV disease prior to BCBM diagnosis. The median number of brain metastases treated per patient was 3 (1 to 12). The median dose of stereotactic radiosurgery (SRS) was 21 Gy (range: 15-24 Gy) treated in a single fraction and for lesions treated with fractionated stereotactic radiation therapy (FSRT) 25 Gy (24-30 Gy) in a median of 5 fractions (range: 3-5). Of the 31 stereotactic sessions, 71% occurred within 1 month of capecitabine. No increased toxicity was noted in our series with no cases of radionecrosis. The 1-year OS, LC, and DIC were 46, 88, and 30%, respectively. CONCLUSIONS: In our single institution experience, we demonstrate stereotactic radiation and capecitabine to be a safe treatment for patients with BCBM with adequate LC. Further study is needed to determine the potential synergy between stereotactic radiation and capecitabine in the management of BCBM.

Trastuzumab Emtansine (T-DM1) and stereotactic radiation in the management of HER2+ breast cancer brain metastases.

BACKGROUND: Due to recent concerns about the toxicity of trastuzumab emtansine (T-DM1) with stereotactic radiation, we assessed our institutional outcomes treating HER2-positive breast cancer brain metastases (BCBM) with T-DM1 and stereotactic radiation. METHODS: This is a single institution series of 16 patients with HER2-positive breast cancer who underwent 18 stereotactic sessions to 40 BCBM from 2013 to 2019 with T-DM1 delivered within 6 months. The Kaplan-Meier method was used to calculate overall survival (OS), local control (LC), distant intracranial control (DIC), and systemic progression-free survival (sPFS) from the date of SRS. A neuro-radiologist independently reviewed follow-up imaging. RESULTS: One patient had invasive lobular carcinoma, and 15 patients had invasive ductal carcinoma. All cases were HER2-positive, while 10 were hormone receptor (HR) positive. Twenty-four lesions were treated with stereotactic radiosurgery (SRS) to a median dose of 21 Gy (14-24 Gy). Sixteen lesions were treated with fractionated stereotactic radiation (FSRT) with a median dose of 25 Gy (20-30Gy) delivered in 3 to 5 fractions. Stereotactic radiation was delivered concurrently with T-DM1 in 19 lesions (48%). Median follow up time was 13.2 months from stereotactic radiation. The 1-year LC, DIC, sPFS, and OS were 75, 50, 30, and 67%, respectively. There was 1 case of leptomeningeal progression and 1 case (3%) of symptomatic radionecrosis. CONCLUSIONS: We demonstrate that stereotactic radiation and T-DM1 is well-tolerated and effective for patients with HER2-positive BCBM. An increased risk for symptomatic radiation necrosis was not noted in our series.