A B S T R A C T PurposeTo evaluate induction chemotherapy with docetaxel, cisplatin, and fluorouracil (TPF) followed by surgery and postoperative radiotherapy versus up-front surgery and postoperative radiotherapy in patients with locally advanced resectable oral squamous cell carcinoma (OSCC). Patients and MethodsA prospective open-label phase III trial was conducted. Eligibility criteria included untreated stage III or IVA locally advanced resectable OSCC. Patients received two cycles of TPF induction chemotherapy (docetaxel 75 mg/m 2 on day 1, cisplatin 75 mg/m 2 on day 1, and fluorouracil 750 mg/m 2 on days 1 to 5) followed by radical surgery and postoperative radiotherapy (54 to 66 Gy) versus up-front radical surgery and postoperative radiotherapy. The primary end point was overall survival (OS). Secondary end points included local control and safety. ResultsOf the 256 patients enrolled onto this trial, 222 completed the full treatment protocol. There were no unexpected toxicities, and induction chemotherapy did not increase perioperative morbidity. The clinical response rate to induction chemotherapy was 80.6%. After a median follow-up of 30 months, there was no significant difference in OS (hazard ratio [HR], 0.977; 95% CI, 0.634 to 1.507; P ϭ .918) or disease-free survival (HR, 0.974; 95% CI, 0.654 to 1.45; P ϭ .897) between patients treated with and without TPF induction. Patients in the induction chemotherapy arm with a clinical response or favorable pathologic response (Յ 10% viable tumor cells) had superior OS and locoregional and distant control. ConclusionOur study failed to demonstrate that TPF induction chemotherapy improves survival compared with up-front surgery in patients with resectable stage III or IVA OSCC.

SUMMARY Controversy exists on the advantages of robotic McKeown esophagectomy (RME) versus thoraco-laparoscopic McKeown esophagectomy (TLME). The aim was to evaluate the short- and mid-term outcomes of RME and TLME in the treatment of patients with esophageal squamous cell carcinoma (ESCC). A consecutive series of 652 patients, 280 in RME and 372 in TLME, who underwent minimally invasive McKeown esophagectomy for ESCC at our department from November 2015 to June 2018 was analyzed. A propensity score-matched comparison with clinicopathological covariates was performed between the two groups. Complications were categorized based on the Esophagectomy Complications Consensus Group (ECCG) recommendation. To identify the recurrence, all patients with R0 resection were followed with a median follow-up period of 20.2 months (range 1–33 months). After propensity score matching, 271 patients were identified for each cohort. In the matched cohorts, two patients died within 90 days in TLME, whereas no patients died in RME. RME was associated with similar intraoperative blood loss (P = 0.895), but with shorter surgical duration (244.5 vs. 276.0 min, P < 0.001), shorter thoracic duration (85.0 vs. 102.9 min, P < 0.001) and lower thoracic conversions (0.7% vs. 5.9%, P = 0.001). In spite of the similar results on total and thoracic lymph nodes dissection, RME yielded more lymph nodes along recurrent laryngeal nerve (4.8 vs. 4.1, P = 0.012), as well as the higher incidence of recurrent nerve injury (29.2% vs. 15.1%, P < 0.001) when compared to TLME. Tumor recurrence occurred in 30 patients and was locoregional only in 9 (3.5%) patients, systemic only in 17 (6.7%) patients, and combined in 4 (1.6%) patients in RME, while in 26 patients and was locoregional only in 10 (10.6%) patients, systemic only in 7 (2.8%) patients, and combined in 9 (3.6%) patients in TLME. RME was associated with a lower rate of mediastinal lymph nodes recurrence (2.0% vs. 5.3%, P = 0.044). Overall and disease-free survival was not different between the two cohorts (P = 0.097 and P = 0.248, respectively). RME was shown to be a safe and oncologically effective approach with favorable short- and mid-term outcomes in the treatment of patients with ESCC.

Objective: To examine the persistence of the original treatment effects 10 years after the Diabetes Control and Complications Trial (DCCT) in the follow-up Epidemiology of Diabetes Interventions and Complications (EDIC) study. In the DCCT, intensive therapy aimed at nearnormal glycemia reduced the risk of microvascular complications of type 1 diabetes mellitus compared with conventional therapy.Methods: Retinopathy was evaluated by fundus photography in 1211 subjects at EDIC year 10. Further 3-step progression on the Early Treatment Diabetic Retinopathy Study scale from DCCT closeout was the primary outcome.Results: After 10 years of EDIC follow-up, there was no significant difference in mean glycated hemoglobin levels (8.07% vs 7.98%) between the original treatment groups. Nevertheless, compared with the former conven-tional treatment group, the former intensive group had significantly lower incidences from DCCT close of further retinopathy progression and proliferative retinopathy or worse (hazard reductions, 53%-56%; PϽ.001). The risk (hazard) reductions at 10 years of EDIC were attenuated compared with the 70% to 71% over the first 4 years of EDIC (PϽ.001). The persistent beneficial effects of former intensive therapy were largely explained by the difference in glycated hemoglobin levels during DCCT. Conclusion:The persistent difference in diabetic retinopathy between former intensive and conventional therapy ("metabolic memory") continues for at least 10 years but may be waning.

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