Katerina Kopeckova

Comparing Clinical Characteristics and Outcomes of Young-onset and Late-onset Colorectal Cancer: An International Collaborative Study

Micro‐Abstract Colorectal cancer in young patients is often diagnosed late, at advanced stages. These patients have more resistant and aggressive disease, despite similar clinical treatment patterns compared with those with late‐onset disease. Background Compared with the general population, the incidence of young‐onset (YO) colorectal cancer (CRC) is increasing. However, a significant knowledge gap exists in the clinical characteristics, treatment patterns, and outcomes for these patients. Materials and Methods Six international tertiary cancer centers conducted a retrospective study. Patients with YO CRC (aged 18‐44 years) and LO CRC (aged > 44 years) diagnosed with histologically proven colorectal adenocarcinoma from June 2003 to June 2014 were enrolled. Patients were randomly chosen from each centers database, and the patient demographics and treatment information were collected. The data were then centralized, and the final analysis was performed at a single institution. Cox proportional hazards models were used to estimate the crude and adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) for progression‐free survival and mortality, and YO was compared with LO. Site‐specific HRs were pooled using a random‐effects meta‐analysis. Results Overall, 498 patients, including 224 with YO (129 men; mean age, 37 ± 5.5 years) and 274 with LO (167 men; mean age, 64.8 ± 9.5 years) CRC, were included. At the diagnosis, 137 patients (61.2%) and 122 patients (44.5%) with YO and LO CRC had metastatic disease, respectively. For both cohorts, the 3 most common presenting symptoms were pain, hematochezia, and weight loss. Surgery was performed in 141 YO (63.0%) and 219 LO (79.9%) patients. The longitudinal noncurative treatment patterns were similar, but more biologic therapy was used for these YO patients. The pooled progression‐free survival analysis results for first‐line noncurative treatment favored LO (HR, 1.96; 95% CI, 1.04‐3.68). The mortality analysis showed no significant differences between the 2 groups (YO: HR, 1.53; 95% CI, 0.91‐2.58). Conclusion Despite similar treatment patterns and survival outcomes, YO disease might be clinically more aggressive.

Outcomes of Patients With Long-Term Treatment Response to Vascular Endothelial Growth Factor-Targeted Therapy for Metastatic Renal Cell Cancer

Micro‐Abstract Although targeted therapies are the mainstay of treatment for metastatic renal cell carcinoma there are limited data on the outcomes of patients with long‐term responses. We report the outcomes of a registry‐based study of patients continuously treated with first‐line targeted therapy for at least 24 months. There were clinically important differences in survival between patients who achieved complete response and those with partial response or stable disease. These differences had not been described before and are important for treatment optimization of this patient subgroup. Background: Although targeted therapies with inhibitors of the vascular endothelial growth factor (VEGF) are the mainstay of treatment for metastatic renal cell carcinoma, there are limited data on the outcome of patients with long‐term response to this treatment. Patients and Methods: In a retrospective, registry‐based study, patients continuously treated with first‐line anti‐VEGF agents for at least 24 months were included. In total, 219 patients had evaluable data and were included in the outcome analysis. Results: Median progression‐free survival (PFS) after initiation of first‐line targeted therapy was 39.7 months (95% confidence interval [CI], 35.9‐43.5 months), with 5‐year PFS of 34.2% (95% CI, 27.2%‐41.2%). Median overall survival (OS) reached 79.1 months (95% CI, 65.2‐93.0 months) with the 5‐year OS of 62.1% (95% CI, 54.5%‐69.7%). In this cohort, 28, 103, and 88 patients achieved complete response (CR), partial response (PR), or stable disease (SD) as the best response, respectively. Median PFS and OS were comparable in patients with PR and SD, but significantly longer in patients with CR (log rank test P value for PFS difference < .001 and .009 for OS difference). Conclusion: There are marked differences in PFS and OS between patients who receive long‐term anti‐VEGF treatment, achieving CR and non‐CR as the best clinical response. Patients with non‐CR experienced a relatively high progression rate shortly after the landmark time point of 2 years.

Paclitaxel‐Loaded Polylactide/Polyethylene Glycol Fibers with Long‐Term Antitumor Activity as a Potential Drug Carrier for Local Chemotherapy

Local application of anticancer agents prolongs the presence time and increases the concentration of drug in the target place and therefore may reduce serious side effects compared to drug systemic administration. The preparation of fibrous materials of polylactide (PLA) and polyethylene glycol (PEG) loaded with paclitaxel (PTX, 1 or 10 wt%) is presented. Scanning electron microscopy proves that PTX is homogeneously incorporated into the fibers. The addition of PEG of various molecular weights (6, 20, or 35 kDa) ensures the release of significantly higher amounts of hydrophobic PTX in a prolonged release time compared to the fibers containing PTX only. Present PLA-PEG fibrous carriers can serve as a drug depot for PTX since they exhibit significant toxicity for cancer cell lines in several-day experiment. They are promising for local recurrence therapy, where the initial release is efficient to kill tumor cells and continued release can prevent their subsequent proliferation.

Alpha-fetoprotein kinetics in patients with hepatocellular carcinoma receiving ramucirumab or placebo: an analysis of the phase 3 REACH study

BackgroundPost-hoc analyses of AFP response and progression and their relationship with objective measures of response and survival were performed in patients from REACH.MethodsSerum AFP was measured at baseline and every 3 cycles (2 weeks/cycle). Associations between AFP and radiographic progression and efficacy end points were analysed.ResultsMedian percent AFP increase from baseline was smaller in the ramucirumab than in the placebo arm throughout treatment. Time to AFP progression (HR 0.621; P < 0.0001) and to radiographic progression (HR 0.613; P < 0.0001) favoured ramucirumab. Association between AFP and radiographic progression was shown at 6 (OR 6.44, 95% CI 4.03, 10.29; P < 0.0001) and 12 weeks (OR 2.28, 95% CI 1.47, 3.53; P = 0.0002). AFP response was higher with ramucirumab compared with placebo (P < 0.0001). More patients in the ramucirumab arm experienced tumour shrinkage and AFP response compared with placebo. Survival was longer in patients with AFP response (13.6 months) than in patients without (6.2 months), irrespective of treatment (HR 0.457, P < 0.0001).ConclusionsTreatment with ramucirumab prolonged time to AFP progression, slowed AFP increase and was more likely to induce AFP response. Similar benefits in radiographic progression and response correlated with AFP changes.