Impact of prior bevacizumab therapy on the incidence of ramucirumab-induced proteinuria in colorectal cancer: a multi-institutional cohort study.

BACKGROUND: The association between prior bevacizumab (BEV) therapy and ramucirumab (RAM)-induced proteinuria is not known. We aimed to investigate this association in patients with metastatic colorectal cancer (mCRC). METHODS: mCRC patients who received folinic acid, fluorouracil, and irinotecan (FOLFIRI) plus RAM were divided into with and without prior BEV treatment groups. The cumulative incidence of grade 2-3 proteinuria and rate of RAM discontinuation within 6 months (6M) after RAM initiation were compared between the two groups. RESULTS: We evaluated 245 patients. In the Fine-Gray subdistribution hazard model including prior BEV, age, sex, comorbidities, eGFR, proteinuria ≥ 2 + at baseline, and later line of RAM, prior BEV treatment contributed to proteinuria onset (P < 0.01). A shorter interval between final BEV and initial RAM increased the proteinuria risk; the adjusted odds ratios (95% confidence intervals) for the intervals of < 28 days, 28-55 days, and > 55 days (referring to prior BEV absence) were 2.60 (1.23-5.51), 1.51 (1.01-2.27), and 1.04 (0.76-1.44), respectively. The rate of RAM discontinuation for ≤ 6M due to anti-VEGF toxicities was significantly higher in the prior BEV treatment group compared with that in the no prior BEV treatment group (18% vs. 6%, P = 0.02). Second-line RAM discontinuation for ≤ 6M without progression resulted in shorter overall survival of 132 patients with prior BEV treatment (P < 0.01). CONCLUSION: Sequential FOLFIRI plus RAM after BEV failure, especially within 55 days, may exacerbate proteinuria. Its escalated anti-VEGF toxicity may negatively impact the overall survival.

Eye tracking in an everyday environment reveals the interpersonal distance that affords infant-parent gaze communication.

The unique morphology of human eyes enables gaze communication at various ranges of interpersonal distance. Although gaze communication contributes to infants' social development, little is known about how infant-parent distance affects infants' visual experience in daily gaze communication. The present study conducted longitudinal observations of infant-parent face-to-face interactions in the home environment as 5 infants aged from 10 to 15.5 months. Using head-mounted eye trackers worn by parents, we evaluated infants' daily visual experience of 3138 eye contact scenes recorded from the infants' second-person perspective. The results of a hierarchical Bayesian statistical analysis suggest that certain levels of interpersonal distance afforded smooth interaction with eye contact. Eye contacts were not likely to be exchanged when the infant and parent were too close or too far apart. The number of continuing eye contacts showed an inverse U-shaped pattern with interpersonal distance, regardless of whether the eye contact was initiated by the infant or the parent. However, the interpersonal distance was larger when the infant initiated the eye contact than when the parent initiated it, suggesting that interpersonal distance affects the infant's and parent's social look differently. Overall, the present study indicates that interpersonal distance modulates infant-parent gaze communication.

Impact of prior bortezomib therapy on the incidence of lenalidomide-induced skin rash in multiple myeloma: a propensity score-matched multi-institutional cohort study.

This retrospective cohort study was conducted to investigate the association between prior bortezomib (BOR) therapy and lenalidomide (LEN)-induced rash in multiple myeloma (MM) patients. Eligible MM patients initially treated with LEN were divided into two propensity score-matched cohorts according to the presence or absence of prior BOR therapy. The primary endpoint of the study was rash incidence. We evaluated 144 patients and each cohort contained 43 patients after matching propensity-score. Rash incidence significantly decreased in patients with prior BOR therapy than in those without (30% vs. 53%, p < .05). Moreover, patients with rash showed a significantly higher incidence of eosinophilia within 1 month after LEN initiation than those without rash. Our findings indicate that prior BOR therapy may reduce the incidence of LEN-induced rash, which may be characterized by eosinophilia. Accordingly, in patients who discontinued LEN therapy due to rash, LEN re-treatment may be successful after BOR therapy.

Oral mucositis associated with anti-EGFR therapy in colorectal cancer: single institutional retrospective cohort study.

BACKGROUND: Chemotherapy-induced oral mucositis impairs the quality of life. The difference in severity of oral mucositis between different anti-epidermal growth factor receptor (EGFR) antibodies combined with cytotoxic drugs in colorectal cancer is unclear. The aim of this study was to investigate the differences in oral mucositis between panitumumab (Pmab) and cetuximab (Cmab) combined with 5-fluorouracil (5-FU). METHODS: We conducted a retrospective cohort study. A total of 75 colorectal cancer outpatients treated with an anti-EGFR antibody combined with FOLFOX, FOLFIRI, or 5-FU/leucovorin as the first- to third-line treatment were included. The primary endpoint was the incidence of grade 2-3 oral mucositis. The secondary endpoint was the time to onset of oral mucositis. We also compared the incidence of toxicities of interest, skin toxicity, hypomagnesaemia and neutropenia, and time to treatment failure (TTF) between the two groups. RESULTS: Thirty-two patients treated with Pmab and 43 patients treated with Cmab were evaluated. Patient characteristics were similar between the two groups. The incidence of grade 2-3 oral mucositis was significantly higher with Pmab than with Cmab (31.3% vs 9.3%, P < 0.05). Moreover, the incidence of grade 3 oral mucositis was significantly higher in patients treated with Pmab (18.8% vs 0%, P < 0.01). The mean (SD) cycles to onset of the worst oral mucositis was 3.0 (2.9) in the Pmab group and 2.3 (1.7) in the Cmab group (P = 0.29). Oral mucositis was characterized by glossitis and cheilitis. The incidences of other toxicities were the following (Pmab vs Cmab): grade 2-3 skin toxicity: 68.8% vs 74.4% (P = 0.61), grade 2-3 hypomagnesaemia: 9.3% vs 7.0% (P = 1.00), grade 3-4 neutropenia: 28.1% vs 37.2% (P = 0.46). The median TTF was not significantly different, i.e., 223 days vs 200 days (P = 0.39) for Pmab vs Cmab. CONCLUSIONS: Pmab-based chemotherapy resulted in significantly higher grades of oral mucositis compared with Cmab-based chemotherapy. The oral condition should be monitored carefully and early supportive care should be provided for patients treated with Pmab-based chemotherapy.