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Background

In colorectal cancer liver metastases (CRCLM), bevacizumab-based neoadjuvant strategies provide increased pathologic response. We aimed at assessing the activity of perioperative capecitabine, oxaliplatin, irinotecan, and bevacizumab (COI-B regimen) in patients with potentially resectable CRCLM, and investigating biomarkers for early prediction of pathologic response.

Patients and Methods

This was a single-center phase II study enrolling patients with liver-limited, borderline resectable disease and/or high-risk features. Patients received 5 preoperative and 4 postoperative cycles of biweekly COI-B (irinotecan 180 mg/m2 and bevacizumab 5 mg/Kg on day 1, oxaliplatin 85 mg/m2 on day 2, and capecitabine 1000 mg/m2 twice a day on days 2 to 6). The primary endpoint was pathologic response rate in the intention-to-treat population. A Simon 2-stage design was adopted to detect an increase from 30% to 50% with a power of 90%. Dynamic imaging biomarkers (early tumor shrinkage [ETS], deepness of response, maximum standardized uptake volume [SUVmax]/regression index) and next generation sequencing data were explored as surrogates.

Results

From June 2013 to March 2017, 46 patients were enrolled. Pathologic response was achieved in 63% patients (endpoint met), and responders achieved significantly better survival outcomes with respect to non-responders. The most frequent grade 3/4 adverse events were diarrhea and neutropenia (8.7%) in the preoperative phase and thromboembolic events (5.9%) in the postoperative phase. ETS and lower SUV-2 were significantly associated with pathologic response.

Conclusion

The COI-B regimen is a feasible and highly active perioperative strategy in patients with molecularly unselected, potentially resectable CRCLM. ETS and SUV-2 have a promising role as imaging-based biomarkers for pathologic response.  相似文献   
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The risk of ventriculostomy-related hemorrhage among patients requiring antiplatelet therapy (AT) for the endovascular treatment of acutely ruptured intracranial aneurysms needed further investigation. The authors performed a systematic review and meta-analysis of the literature examining the EVD-related hemorrhage rate among patients with and without AT (controls). According to PRISMA guidelines, a comprehensive review of studies published between January 1990 and April 2018 was carried out. The authors identified series with > 5 patients reporting the EVD-associated hemorrhage rate among the AT group and the control group. Variables influencing outcomes were analyzed using a random-effects meta-analysis model. We included 13 studies evaluating 516 (with AT) and 647 (without AT) patients requiring ventriculostomy. EVD-related hemorrhage rates were higher among the AT group (125/516 = 20.9%, 95% CI = 11.9–30%, I2 = 90% vs 57/647 = 9%, 95% CI = 5.5–12.5%, I2 = 45.8%) (p < 0.0001). Major EVD-associated hemorrhage rates were low in both the AT and control group (25/480 = 4.4%, 95% CI = 1.7–7.7%, I2 = 53.9% vs 6/647 = 0.7%, 95% CI = 0.03–1.7%, I2 = 0%) (p < 0.0001). Ventriculostomy before embolization and intraprocedural AT were associated with lower rates of EVD-related bleeding (32/230 = 9.6%, 95% CI = 2.1–17.1%, I2 = 75.4% vs 6/24 = 25.1%, 95% CI = 8.8–41%, I2 = 0%) (p < 0.02). The rate of major hemorrhage was higher after dual AT (CP + ASA) compared to single AT (ASA or CP) used as an intraprocedural loading dose (13/173 = 7%, 95% CI = 3.3–10.7%, I2 = 0% vs 6/210 = 1.7%, 95% CI = 0.1–3.4%, I2 = 0%) (p < 0.009). AT during endovascular treatment of acutely ruptured intracranial aneurysms increases the risk of EVD-related hemorrhages, although most of them are small and asymptomatic. When ventriculostomy is performed before endovascular procedures requiring antiplatelet administration, the hemorrhagic risk is minimized. A single antiplatelet therapy is associated with a lower rate of major bleeding than a dual therapy.  相似文献   
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