Chemotherapy remains a primary treatment for metastatic cancer, with tumor response being the benchmark outcome marker. However, therapeutic response in cancer is unpredictable due to heterogeneity in drug delivery from systemic circulation to solid tumors. In this proof-of-concept study, we evaluated chemotherapy concentration at the tumor-site and its association with therapy response by applying a mathematical model. By using pre-treatment imaging, clinical and biologic variables, and chemotherapy regimen to inform the model, we estimated tumor-site chemotherapy concentration in patients with colorectal cancer liver metastases, who received treatment prior to surgical hepatic resection with curative-intent. The differential response to therapy in resected specimens, measured with the gold-standard Tumor Regression Grade (TRG; from 1, complete response to 5, no response) was examined, relative to the model predicted systemic and tumor-site chemotherapy concentrations. We found that the average calculated plasma concentration of the cytotoxic drug was essentially equivalent across patients exhibiting different TRGs, while the estimated tumor-site chemotherapeutic concentration (eTSCC) showed a quadratic decline from TRG = 1 to TRG = 5 (p < 0.001). The eTSCC was significantly lower than the observed plasma concentration and dropped by a factor of ~5 between patients with complete response (TRG = 1) and those with no response (TRG = 5), while the plasma concentration remained stable across TRG groups. TRG variations were driven and predicted by differences in tumor perfusion and eTSCC. If confirmed in carefully planned prospective studies, these findings will form the basis of a paradigm shift in the care of patients with potentially curable colorectal cancer and liver metastases.

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Background: Most stroke patients have their stroke in the community setting, however a significant minority occur while hospitalized for another condition. Prior studies have noted worse outcomes for in-hospital strokes(IHS) compared to community-onset strokes(COS). IHS are also less likely to receive intravenous thrombolytic therapy. The increased use of mechanical thrombectomy(MT) and distinct eligibility criteria from thrombolysis provide additional therapy options for these patients. We present one of the first comparison of outcomes looking specifically at MT for IHS versus COS. Methods: We performed an IRB-approved, retrospective cross-sectional study on patients who underwent MT at our center for acute ischemic stroke between Jan 2012 and Nov 2017. Variables reviewed included patient demographics, vascular risk factors, symptom recognition time, treatment time, and disability as measured by the Modified Rankin Scale(mRS). Statistical analyses were performed using logistic regression to assess the relationship between IHS versus COS. Results: We studied 334 patients (290 COS and 44 IHS) who were treated with MT for acute ischemic stroke. Patients who presented in-hospital were younger (60.7 vs. 70.4 years; p<0.001). IHS were more likely to have a history of coronary artery disease (48% vs. 25%; p<0.003) and tobacco use (32% vs. 16%; p<0.032), conversely, they had a lower rate of atrial fibrillation (20% vs. 42% p<0.005). No significant difference was noted in history of diabetes, hypertension, and dyslipidemia. IHS treated with MT had lower use of intravenous thrombolysis (14% vs 34%; p<0.006). Patients with IHS had a significantly shorter mean symptom recognition to femoral stick time (p<0.039). In addition, IHS patients had significantly better outcomes at discharge as measured by mRS 0-3 (mRS range, 0-6; lower scores indicating less disability). After adjustment for age and stroke severity (National Institute of Health Stroke Scale) IHS continued to have better outcomes at discharge as measured by mRS 0-3; AOR=4.832; 95% Cl, (1.207-19.348); P< 0.026. Conclusion: In conclusion, time from symptom recognition to MT is faster for IHS vs. COS. In addition, IHS had less disability after mechanical thrombectomy for large vessel occlusion.

observation, 89% believe it is still possible to treat effectively if the CRLM grows on surveillance imaging. Conclusion: While surgical management of dCRLM varies widely, nearly all surgeons use intraoperative ultrasound and mandate recent preoperative imaging. Interestingly, nearly half of the respondents elect for observation with the belief that there remains an opportunity to re-address these lesions in the future.