Correlation Between N-Demethyl Imatinib Trough Concentration and Serious Adverse Reactions in Patients with Gastrointestinal Stromal Tumors: A Retrospective Cohort Study.

BACKGROUND: Imatinib is the first-line treatment for gastrointestinal stromal tumors; however, the clinical prognosis and adverse reactions of patients vary owing to individualized discrepancies in plasma exposure. METHODS: To determine the safe interval for steady-state plasma trough concentrations (C min ) of imatinib and its active metabolite, N-demethyl imatinib (NDI), 328 plasma samples from 273 patients treated with imatinib were retrospectively analyzed. Imatinib C min and NDI C min were tested, and adverse reactions were recorded. The association between imatinib C min , NDI C min , and serious adverse reactions was evaluated. RESULTS: The C min range of imatinib was 209.5-4950.0 ng/mL, with the mean value and SD of 1491.8 ± 731.4 ng/mL. The C min range of NDI was 80.0-2390.0 ng/mL with the mean value and SD of 610.8 ± 281.5 ng/mL. NDI C min was positively correlated with imatinib C min , whereas the ratio of NDI C min to imatinib C min (NDI C min /imatinib C min ) was negatively correlated with imatinib C min . Univariate logistic regression analysis demonstrated that the treatment objective, daily dose, imatinib C min , NDI C min , and imatinib C min + NDI C min were significantly associated with serious adverse reactions. Multivariate logistic regression analysis showed that NDI C min was an independent risk factor for serious adverse reactions, with a threshold of 665 ng/mL. CONCLUSIONS: NDI C min was an independent risk factor for serious adverse reactions, with a threshold of 665 ng/mL. Monitoring NDI C min was beneficial for the rational application of imatinib and individualized treatment of patients with gastrointestinal stromal tumors.

Progression of the tumor in a patient with a gastrointestinal stromal tumor with the PDGFRA exon 12 mutation who received multiple surgeries and multiple lines of tyrosine kinase inhibitor therapies: a case report.

Background: Targeted therapy with tyrosine kinase inhibitors (TKIs) benefits most patients with stromal tumors; however, the effects of TKIs in patients with rare cases of gastrointestinal stromal tumors (GISTs) with platelet-derived growth factor receptor alpha (PDGFRA) exon 12 mutations are unclear. Our report of a case treated with multiline TKIs (included ripretinib) may provide some experience into the future management of rare GIST with PDGFRA 12 exon mutation. Case Description: We report the case of a patient (42-year-old female) with a PDGFRA exon 12-mutated GIST who underwent multiple surgeries and multiple lines of TKI therapy. This patient had intra-abdominal recurrence after imatinib, which was used as the 1st-line targeted drug treatment for 7 months after radical surgery, and had widespread metastases in the abdominal cavity after sunitinib, which was used as the 2nd-line targeted drug treatment for 6 months after the second radical surgery. For this advanced GIST patient with extensive intraperitoneal metastasis and rare PDGFRA 12 exon mutation, we then selected ripretinib as the 3rd-line targeted drug therapy to treat the patient. Up to the last follow-up in September 2021, the patient continued to take drugs without obvious complaints of discomfort or adverse events. Conclusions: This case showed that patients with PDGFRA exon 12-mutated GISTs are less likely to benefit from current conventional TKIs, and ripretinib treatment should be considered preferred to regorafenib or even sunitinib according to each patient's situation. However, the limitation of our case is that the patient's second recurrent lesion was not genetically tested to determine the presence of secondary mutation. Further, if a patient's tumor has a high risk of adverse biological behaviors, such as high mitotic figures, vascular tumor thrombus, succinate dehydrogenase B (SDHB) was negative, and regional lymph node metastasis, consideration should be given to shortening the postoperative follow-up interval to 2 months or even 1 month.

Endoscopic Lateral Neck Dissection (IIA, IIB, III, and IV) Using a Breast Approach: Outcomes From a Series of the First 24 Cases.

INTRODUCTION: In order to avoid large neck scar caused by conventional lateral neck dissection. We have explored and introduced endoscopic lateral neck dissection (IIA, IIB, III, and IV) using a breast approach. Now, we summarized and shared the outcomes of the first 24 cases. MATERIALS AND METHODS: All the patients were treated in our institute from January 2017 to May 2018, and followed-up for more than 1 year. The details of patients and this technique have been summarized and analyzed retrospectively. RESULTS: A series of first 24 cases were successfully managed with this technique, and no cases were converted to an open approach. Among these 24 patients, levels III + IV dissection had been performed in 6 patients and levels II+III+IV dissection had been performed in 18 patients. The mean age, body mass index, and sex were 39.3±10.5 years old, 24.1±3.5, and 2 male/22 female, respectively. The average operative time of total operation and lateral neck dissection was 238.8±37.2 minutes and 128.8±21.1 minutes, respectively. The mean dissected lateral lymph nodes were 5.9±2.2 (level II) in 18 cases and 15.9±3.9 (levels III+IV) in 24 cases. In addition, with no severe complications to date, such as asphyxia, main nerves injury (cervical plexus, vagus nerve, etc.), and permanent hypoparathyroidism, nor permanent recurrent laryngeal nerve injury, and so on. However, unexpectedly, had some mild and common complications like transient hypocalcemia in 4 cases (16.67%), transient horse 1 case (4.2%), controllable lymphatic leakage in 2 cases (8.3%), and controllable jugular vein injury in 2 cases (8.3%). One year after the operation, 1 case found lung metastasis but no local recurrence. In other 23 patients, no recurrence/metastasis and the average of serum thyroglobulin is 3.2±3.8 ng/mL. CONCLUSIONS: This technique can yield adequate oncological dissection for selected patients. Endoscopic thyroidectomy along with lateral neck dissection using a breast approach may provide an option for selected patients who favor avoiding a visible neck incision.

The risk factors about prognosis of 142 GIST patients with recurrence or metastasis: A retrospective study of single centre in Northern China.

PURPOSE: In this retrospective study, we investigated the clinicopathologic features, prognosis as well as the factors contributing to prognosis of patients with metastatic or recurrent gastrointestinal stromal tumors (GISTs). METHODS: A total 142 GIST patients with confirmed metastasis or recurrence with complete clinicopathologic and prognostic data were enrolled as research group, and 278 GISTs patients without metastasis or recurrence as control group between June 2003 and June 2013. RESULTS: Significant differences between research group and control group were revealed, including gender, age, primary tumor sites, tumor diameter, mitosis rate, CD117 expression, risk level, treatment methods and surgical types (p<0.05). Univariate survival analysis suggested that factors with significant influence on prognosis were tumor primary site, tumor diameter, mitosis rate, tumor progression (recurrence or metastasis), and treatment methods (p<0.05). Multivariate survival analysis demonstrated that mitosis and treatment methods were independent prognostic factors for GIST patients with metastatis or recurrence. CONCLUSION: Some factors contributed significantly to the prognosis of GIST patients with metastatis or recurrence, and the combination of surgery and targeted agent should be selected for these patients to improve prognosis.

Gastrointestinal stromal tumor (GIST) with liver metastases: An 18-year experience from the GIST cooperation group in North China.

Approximately 40% to 50% of gastrointestinal stromal tumor (GIST) patients will have recurrence or metastases after resection of the primary lesion, and the most common affected sites will be liver and peritoneum. Imatinib has been considered as the first-line therapy of metastatic GIST. Surgery for metastases is proposed when possible. Furthermore, there are controversies concerning hepatic resection and systemic tyrosin kinase inhibitors (TKIs). The therapeutic conditions and long-term outcome of GIST patients with liver metastases in northern China remain unknown.The clinical, pathological, and follow-up data of 144 GIST patients, who had liver metastases between June 1996 and June 2014 from 3 tertiary cancer centers in northern China, were reviewed.Thirty-two cases (22.2%) had hepatectomy with 23 (23/32, 71.9%) R0 resections and 9 (9/32, 28.1%) R1/R2 resections, respectively. Twenty-three patients were given imatinib postoperatively. Furthermore, 98 (68.1%) patients were given TKIs only to control disease progression, and sunitinib was considered after imatinib failure in 12 patients. The 1-, 3- and 5-year survival rate was 82%, 51%, and 24%, with a median overall survival of 48 months for all patients. Patients who had hepatic resection combined with TKIs had a tendency of improved outcome, and the median survival time was 89 months. This was in contrast to patients who received TKIs only, in which median survival time was 53 months. Patients who received imatinib plus sunitinib had a tendency of longer survival time, compared with patients who received imatinib only (not reached vs 50 months).TKIs combined with hepatic resection had a role in improving the outcome of GIST patients with liver metastases.

Clinical application of modified double tracks anastomosis in proximal gastrectomy.

We compared the outcome of two surgical alimentary canal reconstruction methods after proximal gastrectomy. Three hundred ninety-six patients who underwent a radical proximal gastrectomy were randomized into two groups. Group A was treated with modified double tracks anastomosis, and Group B was treated with esophagus-remnant stomach direct anastomosis. Outcome measures were hematological indices, prognostic nutritional index (PNI), plasma hormone concentrations, and Visick index. The operative times in Groups A and B were 210 ± 53 and 150 ± 75 minutes and the hemorrhage volume was 173 ± 67 and 150 ± 75 mL, respectively. Six months after operation, values of hemoglobin concentration, body weights, and PNI indices were significantly increased in Group A compared with Group B. Levels of gastrin and somatostatin were obviously less than preoperative values and levels of cholecystokinin and motilin were significantly higher than preoperative values in both groups. All patients of Group A were classified into Visick index Grades I and II, whereas only 70.37 per cent of Group B belonged to Visick index Grades I and II postoperatively. The overall 3-year survival rate was not significantly different in both groups. Modified double tracks anastomosis as an alimentary canal reconstructive method for radical proximal gastrectomy showed better outcomes than esophagus-remnant stomach direct anastomosis.