Predictive Role of Executive Function in the Efficacy of Intermittent Theta Burst Transcranial Magnetic Stimulation Modalities for Treating Methamphetamine Use Disorder-A Randomized Clinical Trial.

Background: Repetitive transcranial magnetic stimulation (rTMS) has therapeutic effects on craving in methamphetamine (METH) use disorder (MUD). The chronic abuse of METH causes impairments in executive function, and improving executive function reduces relapse and improves treatment outcomes for drug use disorder. The purpose of this study was to determine whether executive function helped predict patients' responses to rTMS treatment. Methods: This study employed intermittent theta burst stimulation (iTBS) rTMS modalities and observed their therapeutic effects on executive function and craving in MUD patients. MUD patients from an isolated Drug Rehabilitation Institute in China were chosen and randomly allocated to the iTBS group and sham-stimulation group. All participants underwent the Behavior Rating Inventory of Executive Function - Adult Version Scale (BRIEF-A) and Visual Analog Scales (VAS) measurements. Sixty-five healthy adults matched to the general condition of MUD patients were also recruited as healthy controls. Findings: Patients with MUD had significantly worse executive function. iTBS groups had better treatment effects on the MUD group than the sham-stimulation group. Further Spearman rank correlation and stepwise multivariate regression analysis revealed that reduction rates of the total score of the BRIEF-A and subscale scores of the inhibition factor and working memory factor in the iTBS group positively correlated with improvements in craving. ROC curve analysis showed that working memory (AUC = 87.4%; 95% CI = 0.220, 0.631) and GEC (AUC = 0.761%; 95% CI = 0.209, 0.659) had predictive power to iTBS therapeutic efficacy. The cutoff values are 13.393 and 59.804, respectively. Conclusions: The iTBS rTMS had a better therapeutic effect on the executive function of patients with MUD, and the improved executive function had the potential to become a predictor for the efficacy of iTBS modality for MUD treatment. Clinical Trial Registration: ClinicalTrials.gov, identifier: ChiCTR2100046954.

Postoperative Chemoradiotherapy With Capecitabine and Oxaliplatin vs Capecitabine for Stage II to III Rectal Cancer: A Randomized Clinical Trial.

Importance: Several studies have explored the efficacy and toxic effects of concurrent 5-fluorouracil (5-FU)- or capecitabine-based chemoradiotherapy (CRT) with or without oxaliplatin in the neoadjuvant setting. Addition of oxaliplatin to 5-FU or capecitabine elicited similar outcomes but with significantly increased toxic effects; however, there is a need for randomized clinical trials comparing 2 CRT regimens for patients receiving CRT in the adjuvant setting. Objective: To explore the efficacy and toxic effects of oxaliplatin combined with postoperative concurrent capecitabine and radiotherapy (RT) for pathological stage II and III rectal cancer. Design, Setting, and Participants: This multicenter randomized clinical trial enrolled patients from 7 centers in China between April 1, 2008, and December 30, 2015. Patients with pathologically confirmed stage II and III rectal cancer were randomized (1:1) to receive concurrent CRT with capecitabine or capecitabine plus oxaliplatin. Analysis was conducted from December 31, 2019, to March 15, 2020. Interventions: RT comprised 45 to 50 Gy in 25 fractions of 1.8 to 2.0 Gy over 5 weeks. In the capecitabine with RT group, concurrent chemotherapy included 2 cycles of capecitabine (1600 mg/m2) on days 1 to 14 and 22 to 35. The capecitabine and oxaliplatin with RT group received identical postoperative RT to that in the capecitabine with RT group combined with capecitabine (1300 mg/m2) on days 1 to 14 and 22 to 35 and a 2-hour infusion of oxaliplatin (60 mg/m2) on weeks 1, 2, 4, and 5. Patients in both groups received adjuvant chemotherapy (capecitabine or fluorouracil and oxaliplatin) after CRT. Main Outcomes and Measures: The primary end point was 3-year disease-free survival (DFS). Results: A total of 589 patients (median [IQR] age, 55 [47-52] years; 375 [63.7%] men and 214 [36.3%] women) were enrolled, including 294 patients randomized to the capecitabine with RT group and 295 patients randomized to the capecitabine and oxaliplatin with RT group. Median (IQR) follow-up was 68 (45-96) months. Most patients had stage III disease (574 patients [75.9%]). Three-year DFS was 76.3% for the capecitabine with RT group and 74.1% for the capecitabine and oxaliplatin with RT group, and 5-year DFS was 72.0% for the capecitabine with RT group and 71.1% for the capecitabine and oxaliplatin with RT group (hazard ratio [HR], 1.07; 95% CI, 0.79-1.44; P = .68). There was no significant difference between groups in overall survival (HR, 0.93; 95% CI, 0.64-1.34; P = .70) or local recurrence (HR, 0.61; 95% CI, 0.31-1.22; P = .16). More grade 3 and 4 acute toxic effects were observed in the capecitabine and oxaliplatin with RT group than in the capecitabine with RT group (114 patients [38.6%] vs 84 patients [28.6%]; P = .01). Conclusions and Relevance: This randomized clinical trial found that addition of oxaliplatin to capecitabine-based postoperative CRT did not improve the efficacy of treatment but increased the risk of severe acute toxic effects. This finding highlights the basic role of postoperative capecitabine with RT for patients with locally advanced rectal cancer. Trial Registration: ClinicalTrials.gov Identifier: NCT00714077.

Prospective phase II trial of nimotuzumab in combination with radiotherapy and concurrent capecitabine in locally advanced rectal cancer.

PURPOSE: The aim of the study was to evaluate the safety and efficacy of adding concurrent nimotuzumab to preoperative radiotherapy with concurrent capecitabine in locally advanced rectal cancer. METHODS AND MATERIALS: Patients with rectal cancer (clinical stage T3/4 or N+) were scheduled to receive weekly nimotuzumab (400 mg; days -6, 1, 8, 15, 22, and 29). Capecitabine (825 mg/m(2)) was delivered orally twice daily for the duration of radiotherapy. Radiotherapy was administered at 50.4 Gy (45 + 5.4 Gy). The main endpoint was the pathologic complete response (pCR) rate. RESULTS: Twenty-one patients with T3 or T4 disease were enrolled; 66.7 % were nodal-positive; the median distance from the anal verge was 5.5 cm. A pCR was achieved in four patients (19.0 %); 71.4 % patients obtained moderate or good tumor regression (Grade 2 and 3). Downstaging occurred in 15/21 (71.4 %) patients by T stage and 11/14 (78.6 %) by N stage. The actual dose intensities (median/mean, %) were nimotuzumab (100, 100) and capecitabine (100, 99.5). The most frequent Grade 1/2 toxicities were radiation dermatitis (57.1 %), nausea/vomiting (52.4 %), leukocytopenia (47.6 %), diarrhea (47.6 %), and proctitis (38.1 %). Grade 3 diarrhea was observed in 9.5 % of patients and Grade 3 leukocytopenia in 4.8 %. CONCLUSION: These preliminary results indicate that nimotuzumab can be safely combined with radiotherapy plus concurrent capecitabine. The efficacy of this regimen (pCR = 19.0 %) was significantly higher than that observed in previous phase II trials of preoperative radiotherapy with concurrent capecitabine and cetuximab in rectal cancer. Further investigation of concurrent nimotuzumab with radiotherapy plus capecitabine is warranted.

Treatment of high-risk gastric cancer postoperatively using intensity-modulated radiotherapy: a single-institution experience.

BACKGROUND/AIMS: The aim of this study was to determine the efficacy and acute toxicity of our early experience with treating postoperatively non-metastatic gastric cancer with intensity-modulated radiotherapy (IMRT). METHODOLOGY: A retrospective review was performed on 47 consecutive patients with gastric cancer and treated with postoperatively adjuvant IMRT at Department of radiation oncology, Zhejiang cancer hospital, China, between January 2007 and August 2009. One patient who did not complete his radiation course was excluded, leaving 46 patients for analyses. The median radiation dose delivered was 4500cGy using 180cGy fractions. Concurrent chemotherapy administered were 5-fluorouracil (n=36), capecitabine (n=9) and none (n=1). RESULTS: The median follow-up time was fifteen months (range 6-28 months). 1-year OS and 2-year OS were 98.0% and 80.0%, assessed by Kaplan-Meier methods. Of the six patients who died, five (83.3%) developed a distant metastases. The overall survival time by tumor size was significantly different (>6cm vs. =6cm, p<0.05). There was no significant survival difference between 5-fluorouracil group and capecitabine group (p=0.80). CONCLUSIONS: The data support the use of IMRT in the adjuvant treatment in high risk gastric cancer postoperatively. Acute toxicity is tolerable. Capecitabine with concurrent IMRT was as effective and tolerable as 5-FU/IMRT. Distant metastasis was the main reason of treatment failure that must be addressed in future trials.

Histidine enhances carbamazepine action against seizures and improves spatial memory deficits induced by chronic transauricular kindling in rats.

AIM: To investigate whether histidine can enhance the anticonvulsant efficacy of carbamazepine (CBZ) and simultaneously improve the spatial memory impairment induced by transauricular kindled seizures in Sprague-Dawley rats. METHODS: Chronic transauricular kindling was induced by repeated application of initially subconvulsive electrical stimulation through ear-clip electrodes once every 24 h until the occurrence of 3 consecutive clonic-tonic seizures. An 8-arm radial maze (4 arms baited) was used to measure spatial memory, and histamine and gamma-amino-butyric acid levels were measured by high performance liquid chromatography (HPLC). RESULTS: Chronic transauricular kindling produced a significant impairment of spatial memory and a marked decrease in histamine content in the hypothalamus, the brainstem, and the hippocampus. Injection of histidine (1000 mg/kg or 1500 mg/kg, ip) significantly inhibited transauricular kindled seizures. Injection of histidine at lower doses (200 mg/kg or 500 mg/kg, ip) had no appreciable anticonvulsant effect when administered alone, whereas it significantly potentiated the protective effects of CBZ against kindled seizures. CBZ had no ameliorative effect on memory deficit, but, in contrast, histidine (200 mg/kg or 500 mg/kg, ip) alone or co-administered with CBZ significantly ameliorated the memory deficits induced by the seizures. CONCLUSION: Chronic transauricular kindling is a very useful animal model for evaluating memory deficits associated with epilepsy, and histidine has both a potentiate effect on the anticonvulsant efficacy of CBZ and an ameliorative effect on the spatial memory deficits induced in this model. Histidine at a specific dosage range might serve as a beneficial adjuvant for the clinical treatment of epilepsy, especially when accompanied by impaired spatial memory.