Background In the existing next generation sequencing (NGS) system, epidermal growth factor receptor (EGFR) exon 19 deletion-insertion (19delins) is still interpreted into the category of EGFR exon 19 deletion (19del). However, the controversy exists whether the two mutation types have the similar responses and resistant mechanisms to first-generation EGFR tyrosine kinase inhibitor (TKI) in non-small cell lung cancer (NSCLC) patients. Methods We successively and retrospectively reviewed the NGS data of 3054 patients diagnosed as advanced NSCLC from November 2017 to September 2020. Finally, 41 patients with EGFR 19delins mutation and 41 patients with EGFR 19del mutation who received first-generation EGFR TKIs as first-line therapy were included in the study. Results A total of 17 genotypes were identified in this study, including L747_P753delinsS (10/41), L747_A750delinsP (9/41), L747_T751delinsP (6/41) and E746_S752delinsV (3/41). Under the same baseline characteristics, the population of EGFR 19delins respond well to first line EGFR TKIs as well as those of EGFR 19del, with little difference in median progression-free survival (mPFS): 10.4 months vs. 13.1 months, p = 0.1076). Interestingly, patients with L747_T751delinsP seem to have a better mPFS than others (18.7 months vs. 13.1 months, p = 0.035). After the disease progression, both EGFR 19delins and EGFR 19del had similar rates of developing EGFR T790M mutation resistance (45.8% vs. 57.8%), and those receiving osimeritinib as second-line treatment obtain the similar survival benefits (mPFS: 12.0 months vs. 12.2 months (p = 0.97). Conclusions This retrospective cohort study furnish the evidence that therapeutic responses and survival of untreated NSCLC population with EGFR 19delins mutation are equal to those with common EGFR 19del mutation after administration of EGFR TKIs therapy.
Primary spinal cord glioblastoma multiforme (scGBM) is an uncommon entity in pediatrics, and intracranial metastasis originating in spinal cord gliomas is very rare. A 7-year-old female presented with weakness in the limbs, paralysis of the lower limbs and incontinence. The initial MRI of the spinal cord revealed expansion and abnormal signals from T2 to T5. She was initially diagnosed with Neuromyelitis optica spectrum disorders and treated with high-dose glucocorticoid and gamma globulin. Four months later, her symptoms worsened and follow-up imaging showed multiple intracranial mass lesions. We performed a subtotal resection of the right thalamic basal ganglia tumor and gross total resection of the right frontal lobe tumor under microscopic examination. Histopathology revealed scGBM with intracranial metastasis and the molecular pathology diagnosis suggested H3K27M mutant diffuse midline glioma WHO grade IV, which had previously been misdiagnosed as a Neuromyelitis optica spectrum disorders. We review the literature of intracranial metastases originating from pediatric primary spinal cord glioblastoma multiforme and summarize possible methods of differentiation, including changes in muscle strength or tone, intramedullary heterogeneously enhancing solitary mass lesions and cord expansion in MRI. Finally, we emphasize that in unexpected radiological changes or disadvantageous response to the treatment, a biopsy to achieve a pathological diagnosis is necessary to discard other diseases, especially neoplasms.
Craniopharyngiomas (CPs) are benign tumors arising from the sellar region. However, little is known about their clinical features and long-term recurrence due to low morbidity and the lack of large cohort studies. Thus, we aimed to develop nomograms to accurately predict the extent of resection and tumor recurrence using clinical parameters. A total of 545 patients diagnosed with CP between 2009 and 2019 were examined: 381 in the development cohort and 164 in the validation cohort. Least absolute shrinkage and selection operator (LASSO) and Cox regression analyses were performed to establish two nomograms. Receiver operating characteristic (ROC) curves, calibration curves, decision curve analysis (DCA) and Kaplan-Meier (KM) curves were used to evaluate their predictive performance and discriminative power, respectively, in the two cohorts. In addition, the EORTC QLQ-BN20 questionnaire was used to assess neuropsychological status in the follow-up. In the development cohort, the area under the curve (AUC) and C-index were 0.760 and 0.758, respectively, for predicting the extent of resection and 0.78 and 0.75, respectively, for predicting 3-year progression-free survival (PFS) and 5-year PFS. Additionally, the model had a predictive accuracy of 0.785. Both nomograms showed acceptable discrimination in the two cohorts. Moreover, DCA demonstrated excellent clinical benefits from the two nomograms. Finally, participants were classified into two distinct risk groups according to the risk score, and an online calculator was created for convenient clinical use. During long term follow-up, hypothyroidism (77.61%) and hypocortisolism (76.70%) were the most common endocrine dysfunction after surgery and significant deficits were observed concerning visual disorder, motor dysfunction and seizures in the recurrent groups. In particular, better quality of life was associated with gross total resection (GTR), postoperative radiation, anterior interhemispheric (AI) approach and transsphenoidal approach. To our knowledge, these are the first nomograms based on a very large cohort of patients with CP that show potential benefits for guiding treatment decisions and long-term surveillance. The current study demonstrated the online calculator serve as the practical tool for individual strategies based on the patient’s baseline characteristics to achieve a better prognosis.
Background: This study is to investigate the effects and resistance mechanisms of first-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) in non-small cell lung cancer (NSCLC) patients carrying rare EGFR exon 19 deletion-insertion (19delins) mutations. Methods: The next generation sequencing (NGS) data of 1783 patients diagnosed as advanced NSCLC from November 2017 to September 2020 were successively and retrospectively reviewed. 41 patients with EGFR 19delins and 41 patients with EGFR exon 19 deletion (19del) were enrolled in this study, who were given first generation EGFR TKIs as first-line therapy. Results: 17 mutation types of EGFR 19delins were identified in this study, L747_P753delinsS (10/41) and L747_A750delinsP (9/41) were the most frequent mutation types, followed by L747_T751delinsP (6/41) and E746_S752delinsV (3/41). Under the same baseline characteristics, median progression-free survival (mPFS) was similar in patients with EGFR 19delins to those with EGFR 19del (10.4 months vs. 13.1 months, p=0.1076). Interestingly, patients with L747_T751delinsP had a better mPFS than those with other variants (18.7 months vs. 13.1 months, p=0.035). No significant difference in mPFS was found among the three groups of gefitinib, icotinib, and erlotinb with 14.7 months, 10.9 months, and 13.1 months (p>0.05). After progression from first-line EGFR TKIs, both EGFR 19delins and EGFR 19del had similar rates of developing resistance mechanisms including EGFR T790M mutation (45.8% vs. 57.8%). Patients acquiring T790M mutation received osimeritinib as second-line treatment, and the mPFS was similar between the groups of EGFR 19delins (n=8) and EGFR 19del (n=10): 12.0 months vs. 12.2 months (p=0.97). Conclusion: Our results indicate that patients with uncommon EGFR 19delins can also benefit from first-generation EGFR TKIs treatment, having similar treatment responses and survival outcomes to those with EGFR 19del, even similar clinical outcomes from osimeritinib upon acquiring T790M resistance mutation.
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