The Prognostic Value of Locoregional Interventions for BRAF V600E Metastatic Colorectal Cancer: A Retrospective Cohort Analysis

The prognostic heterogeneity in patients with BRAF V600E metastatic colorectal cancer (mCRC) remains poorly defined. Real-world data of 93 BRAF V600E mCRC patients from Sun Yat-sen University Cancer Center were evaluated using the prognostic factors affecting overall survival (OS). Treatment of metastases served as an independent prognosticator, where curative locoregional interventions (LRIs) were associated with superior clinical outcomes (adjusted hazard ratio (HR): 0.46, 95% confidence interval (CI): 0.22–0.98; p = 0.044). The LRIs group showed an improved median OS of 49.4 months versus 18.3 months for the palliative treatments (PTs) group. The median OS of patients with colorectal liver metastasis (CRLM) was significantly prolonged after undergoing LRIs (42.4 vs. 23.7 months; HR: 0.11, 95% CI: 0.01–1.22; p = 0.030), and patients in the LRIs plus liver-limited or lung-limited metastasis (LLM) group benefited more than those in the LRIs plus non-LLM group when compared to the PTs group (LLM from LRIs vs. PTs, HR: 0.16, 95% CI: 0.04–0.68; p = 0.006. Non-LLM from LRIs vs. PTs, HR: 0.47, 95% CI: 0.21–1.05; p = 0.074). In conclusion, we confirmed the positive prognostic value of LRIs in BRAF V600E mCRC, particularly in patients with CRLM or LLM.

Predictive and Prognostic Factors of Synchronous Colorectal Lung-Limited Metastasis

Aim. This study is aimed at investigating predictive and prognostic factors of synchronous colorectal lung-limited metastasis (SCLLM) based on The Surveillance, Epidemiology, and End Results (SEER) database. Methods. A multivariate logistic regression model was constructed to identify independent predictors of SCLLM. A multivariate Cox proportional hazards regression model was used to distinguish independent prognostic factors. Results. This study enrolled 168,007 colorectal cancer (CRC) patients without metastatic diseases and 1,298 cases with SCLLM. Eight features, involving race, tumor location, pathological grade, histological type, T stage, N stage, and tumor size as well as CEA, could be used as the independent predictors. As the nomogram shown, the T4 stage contributed the most to SCLLM, followed by the N2 stage, elevated CEA, and rectal cancer. A multivariate regression analysis discriminated 9 independent prognostic factors, including age, race, marital status, pathological grade, T stage, colectomy/proctectomy, chemotherapy, CEA, and TD. The prognostic nomogram illustrated that nonresection/NOS played as the poorest prognostic factor, followed by nonchemotherapy, ≥75-year old and T4 stage. The cumulative survival curves revealed the influence of each prognostic factor on survival after controlling the other variables. Conclusions. This study identified independent predictors and prognostic factors for SCLLM based on a large database of the United States. The predictors and prognostic factors can provide supporting evidence for the prevention and treatment of SCLLM.

RADI-18. STEREOTACTIC RADIOSURGERY OR FRACTIONATED STEREOTACTIC RADIOSURGERY FOR BRAIN METASTASES FROM SMALL CELL LUNG CANCER

BACKGROUND: Current standard of care (SOC) management of the brain differs between non-small cell lung cancer (NSCLC) & small cell lung cancer (SCLC). For SCLC, WBRT is considered SOC, even for solitary metastasis. In the setting of no-known metastases, prophylactic cranial irradiation (PCI) is considered SOC. SRS is occasionally utilized in SCLC, e.g. in setting of limited metastasis after WBRT/PCI, or limited metastasis after excellent systemic response to extracranial therapy, or if patient declines WBRT. In this study, we sought to understand more about the nature and outcomes of patients with SCLC who received intracranial SRS at our institution. METHODS: We reviewed radiosurgery treatments from 2005 thru 2019 for patients with SCLC who received SRS. Variables included were: time interval between diagnosis/SRS and death, prior WBRT/ PCI, number of targets, performance status, modality (GK or linac), prior surgery, and available follow-up. RESULTS: We identified 92 SRS treatments among 74 patients. 30 received upfront SRS, the remainder as post-WBRT/PCI salvage. Median survival after initial diagnosis was 22.0 months (min = 6.6, max 55.4). Median survival after first SRS was 6.1 months (min = 0.5, max = 40.4). Median recorded KPS was 75.6. Mean number of mets treated was 3.4 (min = 1, max = 12). Prescription dose range was 12 to 20Gy in single fraction, and 25 to 30Gy in five fraction treatment. 53 treatments were performed on Gamma Knife, 37 with linear accelerator. Four patients were treated post-operatively, one patient was treated pre-operatively. CONCLUSIONS: Survival in our cohort of SCLC patients receiving intracranial SRS compared favorably with historical SCLC controls (8-13mo after dx). Future work will seek to clarify whether there is a difference in brain metastasis velocity between patients treated with upfront PCI/WBRT or SRS, and also seek to address the minimum necessary dose to control SCLC metastases.

Liver and/or lung metastasectomy after cetuximab or bevacizumab+FOLFIRI chemotherapy in patients (pts) with metastatic colorectal cancer (mCRC).

843 Background: Some mCRC pts who have liver and/or lung metastases (LLMs) could achieve cure after palliative chemotherapy and conversion surgery (CS) including metastasectomy. Though targeted agents including bevacizumab and cetuximab significantly improved outcomes in mCRC pts, the effect of targeted agents on cure rate after CS has not yet been thoroughly investigated. Methods: We analyzed clinical data of mCRC pts who initially had unresectable LLMs regardless of their size and number and underwent first-line cetuximab or bevacizumab+FOLFIRI. Pts who had metastasis other than liver and lung were excluded. Results: From January 2013 to May 2016, 87 pts (male, 56) were consecutively enrolled: liver-limited metastasis in 42 pts (48.3%), lung-limited metastasis in 17 pts (19.5%), and both liver and lung metastases in 28 pts (32.2%). Median age was 62 years (range, 37-85). K-RAS or N-RAS mutation was detected in 39 pts (46.4%) and B-RAF in 2 pts (3.1%) among mutation evaluated pts. Among them, 35 pts (40.2%) received cetuximab+FOLFIRI and the others (N = 52, 59.8%), bevacizumab+FOLFIRI. Median follow-up time was 20.0 months (range, 1.9-49.1). Response rate was 65.7% in the cetuximab group (CET) and 42.3% in the bevacizumab group (BEV) ( p= 0.032). Median progression-free survival was 19.1 months (95% confidence interval [CI], 11.2-27.1) in CET and 14.1 months (95% CI, 11.5-16.8) in BEV ( p= 0.249). CS was performed in 24 pts (27.6%) after median 8.7 months (range, 2.5-27.3) after initiation of chemotherapy. In CET, 11 pts (31.4%) including 8 pts with partial response (PR) and 3 pts with stable disease (SD) underwent CS and all (100%) attained R0. In BEV, 13 pts (25%) including 6 pts with PR and 7 pts with SD received CS and 11 of them (84.6%) achieved R0. Among pts with R0 resection, median disease-free survival (DFS) was 8.8 months (95% CI, 4.9-12.7) in CET and 3.2 months (95% CI, 0.0-7.4) in BEV ( p= 0.326). Conclusions: A substantial proportion of pts could receive CS after cetuximab or bevacizumab+FOLFIRI chemotherapy. CET tended to show higher rate of CS. However, the median DFS after R0 resection was not significantly different between the two groups.

Fate of disappeared hepatic metastasis after mFOLFOX6 plus bevacizumab therapy.

e14127 Background: Neoadjuvant and conversion chemotherapy for liver limited metastasis from colorectal cancer (CRC) is a current topic. Minute liver metastasis sometimes disappears on preoperative imaging and intraoperative examination (including contrast enhanced intraoperative ultrasonography (CEIOUS)) after chemotherapy using highly effective regimen, such as FOLFOX or FOLFIRI with molecular targeted agent. We reported a high pathological complete response (CR) rate of resected liver metastasis from CRC after preoperative mFOLFOX6 plus bevacizumab (Bmab) therapy (AACR 2011, abstract #3218), but It is still unclear whether disappeared lesions after chemotherapy need to be removed. Methods: Out of 17 patients with liver limited metastasis from CRC treated with mFOLFOX6 plus Bmab therapy, 9 patients (52%) underwent liver resection after chemotherapy. In 6 of the 9 patients, one or more disappeared lesion(s) after the chemotherapy was not resected and followed up by enhanced CT once every 3 months. Follow up period was 9 to 33 months (22 months in median). Results: Before chemotherapy, 53 liver metastases were detected in the 6 patients. After chemotherapy, 29 (55%) lesions were not detected by preoperative CT or CEIOUS. All the 24 lesion, which were pointed out at the operation, were resected. By histological examination, no viable tumor cell was observed in 12 lesions (50%) among resected lesions. In follow up period, in situ recurrence occurred in 5 lesions (17%) in 4 patients. Three of the 4 patients underwent curative resection of re-detected liver metastases. Conclusions: It was reported that cancer cells remain over 80% of clinically disappeared lesion after conventional chemotherapy. In the present study, only 17% of disappeared lesion after mFOLFOX6 plus Bmab therapy caused in situ recurrence. With this result and a high pathological CR rate of the resected liver metastases after mFOLFOX6 plus Bmab therapy, it is speculated that complete resection for disappeared lesions after this chemotherapy is not always necessary.