Treatment-specific risk of subsequent malignant neoplasms in five-year survivors of diffuse large B-cell lymphoma.

BACKGROUND: The introduction of rituximab significantly improved the prognosis of diffuse large B-cell lymphoma (DLBCL), emphasizing the importance of evaluating the long-term consequences of exposure to radiotherapy, alkylating agents and anthracycline-containing (immuno)chemotherapy among DLBCL survivors. METHODS: Long-term risk of subsequent malignant neoplasms (SMNs) was examined in a multicenter cohort comprising 2373 5-year DLBCL survivors treated at ages 15-61 years in 1989-2012. Observed SMN numbers were compared with expected cancer incidence to estimate standardized incidence ratios (SIRs) and absolute excess risks (AERs/10 000 person-years). Treatment-specific risks were assessed using multivariable Cox regression. RESULTS: After a median follow-up of 13.8 years, 321 survivors developed one or more SMNs (SIR 1.5, 95% CI 1.3-1.8, AER 51.8). SIRs remained increased for at least 20 years after first-line treatment (SIR ≥20-year follow-up 1.5, 95% CI 1.0-2.2, AER 81.8) and were highest among patients ≤40 years at first DLBCL treatment (SIR 2.7, 95% CI 2.0-3.5). Lung (SIR 2.0, 95% CI 1.5-2.7, AER 13.4) and gastrointestinal cancers (SIR 1.5, 95% CI 1.2-2.0, AER 11.8) accounted for the largest excess risks. Treatment with >4500 mg/m2 cyclophosphamide/>300 mg/m2 doxorubicin versus ≤2250 mg/m2/≤150 mg/m2, respectively, was associated with increased solid SMN risk (hazard ratio 1.5, 95% CI 1.0-2.2). Survivors who received rituximab had a lower risk of subdiaphragmatic solid SMNs (hazard ratio 0.5, 95% CI 0.3-1.0) compared with survivors who did not receive rituximab. CONCLUSION: Five-year DLBCL survivors have an increased risk of SMNs. Risks were higher for survivors ≤40 years at first treatment and survivors treated with >4500 mg/m2 cyclophosphamide/>300 mg/m2 doxorubicin, and may be lower for survivors treated in the rituximab era, emphasizing the need for studies with longer follow-up for rituximab-treated patients.

Long-term neurodevelopmental impairment in neonates surgically treated for necrotizing enterocolitis: enterostomy associated with a worse outcome.

BACKGROUND: Necrotizing enterocolitis (NEC) patients often have neurodevelopmental impairment, but the long-term follow-up data is limited. We determined whether surgical factors were of prognostic value for long-term neurodevelopment in children surviving surgery for NEC (SNEC). PATIENTS AND METHODS: SNEC patients born between 1996 and 2002 were tested for verbal (VIQ), performance (PIQ) and total (TIQ) intelligence using Wechsler's Intelligence Scale for Children, Third Edition, Dutch Version, and motor skills using the Movement Assessment Battery for Children (M-ABC). Neonatal and surgical data were obtained retrospectively to assess prognostic factors. RESULTS: 19 patients (12 boys), median age 9.9 years (range 6.2-13.1), gestational age 31.0 weeks (range 25.2-40), birth weight 1 250 g (range 780-3 175) were evaluated. Infants with an enterostomy (n=14) scored lower on intelligence than children with a primary anastomosis (n=5): VIQ 85 ± 12 vs. 101 ± 15, p=0.04; PIQ 79 ± 13 vs. 92 ± 11, p=0.06; TIQ 82 ± 11 vs. 97 ± 13, p=0.04. Motor skills were either suspect or clinically impaired in 74%. Clinical classification of results suggest more children in the enterostomy group had a performance rated as clinically impaired compared to the primary anastomosis group, although no statistical difference in M-ABC score was found. There were no differences between primary anastomosis and enterostomy patients with regard to gestational age, birth weight, comorbidities, preoperative Bell stage, residual small and large bowel lengths, inotropic medication, duration of ventilatory support, NICU and hospital stay, and physical exam data on follow-up. However, a selection bias could not be ruled out. CONCLUSIONS: The results suggest that an enterostomy in SNEC patients could be associated with worse neurodevelopmental outcomes by the age of 6-13 years compared to a primary anastomosis, although the severity of illness was comparable between both groups. Further studies are needed to prevent selection bias and to elucidate the impact of abdominal surgical factors on neurodevelopmental outcome and the underlying pathophysiology.