Wu, Shengjie

Abstract Background The study aimed to evaluate whether simplified chemotherapy followed by dose-reduced irradiation was effective for treating patients (ages 3–21 years) with localized germinoma. The primary endpoint was 3-year progression-free survival (PFS) rate. Methods Patients with a complete response to chemotherapy with carboplatin and etoposide received 18 Gy WVI + 12 Gy boost to the tumor bed. Patients with partial response proceeded to 24 Gy WVI + 12 Gy. Longitudinal cognitive functioning was evaluated prospectively on ALTE07C1 and was a primary study aim. Results One hundred and fifty-one patients were enrolled; 137 were eligible. Among 90 evaluable patients, 74 were treated with 18 Gy and 16 with 24 Gy WVI. The study failed to demonstrate noninferiority of the 18 Gy WVI regimen compared to the design threshold of 95% 3-year PFS rate, where, per design, patients who could not be assessed for progression at 3 years were counted as failures. The Kaplan-Meier (KM)-based 3-year PFS estimates were 94.5 ± 2.7% and 93.75 ± 6.1% for the 18 Gy and 24 Gy WVI cohorts, respectively. Collectively, estimated mean IQ and attention/concentration were within normal range. A lower mean attention score was observed at 9 months for patients treated with 24 Gy. Acute effects in processing speed were observed in the 18 Gy cohort at 9 months which improved at 30-month assessment. Conclusions While a failure according to the prospective statistical noninferiority design, this study demonstrated high rates of chemotherapy responses, favorable KM-based PFS and OS estimates in the context of reduced irradiation doses and holds promise for lower long-term morbidities for patients with germinoma.

Abstract Aims His–Purkinje conduction system pacing (HPCSP) utilizing His (HBP) or left bundle branch pacing (LBBP) in patients with atrial fibrillation (AF) and wide QRS duration has not been well studied. We assessed the benefit of left bundle branch block (LBBB) correction during HPCSP in AF patients undergoing atrioventricular junction (AVJ) ablation with LBBB, compared with those with narrow QRS duration. Methods and results This is an observational study in consecutive patients with typical LBBB or narrow QRS duration in whom we attempted HPCSP after AVJ ablation for refractory AF with a left ventricular ejection fraction (LVEF) ≤ 50%. Echocardiographic responses and clinical outcomes were assessed at baseline and during 1 year of follow-up. A total of 178 patients were enrolled, of which 170 achieved AVJ ablation + permanent HPCSP (age 69.3 ± 10.1 years; LVEF 34.3 ± 7.7%), 133 (78.2%) patients had a narrow QRS duration, and 37 (21.2%) had an LBBB. The QRS duration changed from a baseline of 159.7 ± 16.6 ms to a paced QRS duration of 110.4 ± 12.7 ms in the LBBB cohort and from 95.6 ± 10.4 to 100.8 ± 14.5 ms (both P < 0.001) in the narrow QRS cohort after AVJ ablation and pacing. Compared with the narrow QRS cohort, the LBBB cohort showed a greater absolute increase in LVEF (+22.3% vs. +14.2%, P < 0.001), higher super responder rate (71.4% vs. 49.2%, P = 0.011), and greater New York Heart Association (NYHA) class improvement (−1.9 vs. −1.4, P < 0.001) at 1 year. Conclusion Patients with LBBB have greater improvement in LVEF and NYHA class function than patients with narrow QRS from HPCSP after AVJ ablation.