Abstract We analyzed the impact of the diagnosis-to-treatment interval (DTI) on survival in patients with CD5-positive diffuse large B-cell lymphoma (CD5 + DLBCL), using a data set of newly diagnosed patients. Among the 336 eligible patients, 247 (74%) received R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone), and 89 (26%) were treated with dose-adjusted (DA)-EPOCH-R (etoposide, prednisolone, vincristine, cyclophosphamide, doxorubicin, and rituximab). The median DTI was 18 days (range 0–118). The short DTI (≤ 14 days) group included 135 patients (40%), and the long DTI (> 14 days) group included 201 patients (60%). Compared with the long DTI group, the short DTI group had more aggressive disease characteristics. Both the progression-free survival (PFS) (P = 0.01) and the overall survival (OS) (P < 0.01) were significantly inferior in the short DTI group compared with those in the long DTI group. Among 89 patients who received DA-EPOCH-R, no significant differences in PFS (P = 0.92) or OS (P = 0.86) were observed between the two groups. Multivariate analysis revealed that no DA-EPOCH-R was a risk factor for PFS in the short DTI group (P = 0.06). A short DTI was a negative prognostic factor in our CD5 + DLBCL cohort. DA-EPOCH-R could be considered a potential treatment option for patients with a short DTI.
We thank Dr. Shah for his insightful commentary on our report identifying reduced perfusion pressure (PP) as a predictor of protein-losing enteropathy (PLE) after the Fontan procedure. We agree that PP is an indirect marker and that Fontan-associated PLE is multifactorial, with gut dysbiosis among its contributors. We propose, however, that these downstream changes share a common upstream origin-the chronic hemodynamic burden of the Fontan circulation-and outline an integrated, multidisciplinary approach to clarifying the mechanisms of PLE.
OBJECTIVE:Evaluate long-term efficacy, safety, and tolerability of once-weekly somapacitan, a long-acting growth hormone (GH) derivative, in children born small for gestational age (SGA) with short stature, including after switching from daily GH. DESIGN:REAL5 (NCT03878446) is a global, randomized, open-label, controlled phase 2 study comprising a 26-week main phase, 26-week extension I, and an ongoing 4-year extension II. METHODS:Sixty-two children born SGA with short stature were recruited at 38 clinics across 12 countries and randomized (1:1:1:1:1) to somapacitan (0.16, 0.20, or 0.24 mg/kg/week) or daily GH (0.035 or 0.067 mg/kg/day) until week 52 (inclusive main phase and extension I). Sixty participants entered extension II. Forty-eight participants switched to somapacitan 0.24 mg/kg/week from cohorts randomized to daily GH or lower somapacitan doses. Fifty-five children completed 208 weeks of treatment. Novel safety and efficacy results from week 52 to 208 are presented here. RESULTS:Across all treatment arms, continuous increases in height standard deviation scores were observed from week 52 to week 208, including after switch to somapacitan 0.24 mg/kg/week. The safety and tolerability profile for somapacitan 0.24 mg/kg/week was similar to the well-established safety and tolerability profile for daily GH in SGA. Patient preference questionnaire results indicate that most respondents (87%) prefer somapacitan over daily GH. Most respondents (80%) answered that they expect to be more adherent to treatment with somapacitan. CONCLUSIONS:These results support long-term continuous efficacy, safety, and tolerability of GH therapy with somapacitan 0.24 mg/kg/week for up to 4 years in children born SGA, including after switching from daily GH. CLINICALTRIALS.GOV:NCT03878446.
Background/Objectives: Although Tumor-Treating Fields (TTFields) therapy is an established treatment modality for adult glioblastoma, clinical data on its efficacy in pediatric brain tumors are extremely scarce. The present study aimed to evaluate the safety of TTFields therapy for pediatric diffuse high-grade glioma (HGG) and to conduct an exploratory analysis of its efficacy. Methods: A prespecified, interim analysis was performed to determine whether the study should be continued on the basis of safety and feasibility data on the first three patients. The target population was children aged 5 to 17 years with newly diagnosed, supratentorial HGG or its first recurrence following frontline therapy. After completion of initial, local treatment for the tumor (surgical removal and/or radiotherapy), all patients received TTFields therapy using OptuneTM for 28 days per course for up to 26 courses until disease progression. Results: The interim analysis, which was completed in October 2022, included three female patients aged 14, 17, and 9 years. All had a histological grade 4 tumor, two of which were radiation-induced, secondary HGG. No serious, treatment-related toxicities or device-related issues were observed. All three patients were able to continue using the device for 75% or more of the time in accordance with the protocol, suggesting that the treatment was feasible. The MRI findings of two patients indicated that the treatment has a potential antitumor effect. Based on these results, the study was resumed and is currently being continued at multiple centers. Conclusions: The initial results of the prespecified, interim analysis demonstrated that TTFields therapy was safe and feasible for children with HGG. This study was funded by the Japan Agency for Medical Research and Development (AMED) and was registered with the Japan Registry of Clinical Trials (jRCTs032200423).
The optimal timing of surgery following neoadjuvant therapy in esophageal squamous cell carcinoma (ESCC) remains uncertain. This exploratory analysis aims to assess the impact of time to surgery (TTS) on perioperative and survival outcomes in patients with advanced ESCC enrolled in the phase III trial JCOG1109. Patients who underwent esophagectomy following neoadjuvant chemotherapy or chemoradiotherapy were included. Within each treatment arm, patients were categorized into four TTS subgroups according to cohort quartiles. Perioperative complications, overall survival (OS), and progression-free survival (PFS) were evaluated. The median TTS was 35 (range, 16–81), 38 (17–109), and 41 (14–98) days for the cisplatin plus fluorouracil (CF), docetaxel, cisplatin plus fluorouracil, and CF with radiotherapy (CF-RT) arms, respectively. Baseline characteristics were comparable across the TTS subgroups. Operative time and overall complication rates showed no significant differences. In the CF-RT arm, a longer TTS was associated with increased blood loss (200, 210, 300, and 370 mL) and a trend toward a higher anastomotic leakage (6
