Double-dose osimertinib combined with intrathecal injection of pemetrexed improves the efficacy of EGFR-mutant non-small cell lung cancer and leptomeningeal metastasis: case report and literature review.

Leptomeningeal metastasis (LM) is a complication of non-small cell lung cancer (NSCLC) characterized by poor prognosis and short survival. A variety of therapeutic approaches have been sought to improve the efficacy of LM. Here we present a clinical case and conduct a literature review to investigate the effectiveness and safety of double-dose osimertinib combined with a pemetrexed intrathecal injection. This is an older man who underwent thoracoscopic pneumonectomy and was diagnosed with stage IIA lung adenocarcinoma with EGFR21 L858R mutation. He experienced thoracic vertebral metastases 33 months postoperatively and received first-line treatment with gefitinib combined with radiotherapy for vertebral metastases. However, the patient developed a grade 3 rash with unacceptable toxicity and his CEA levels were significantly increased 22 months later, leading to a targeted treatment adjustment to 80 mg of osimertinib orally once daily. Four months later, the patient developed LM and osimertinib dosage was increased to 160 mg once daily; however, neurological symptoms did not improve, and cerebrospinal fluid (CSF) tumor cells remained detected. Accordingly, the patient received an intrathecal injection of pemetrexed (dose 30 mg) every 2-3 months, 2-3 times per course (4-6 days each time), and continued to receive a double dose of osimertinib. After three courses of intrathecal chemotherapy, CSF tumor cells were eliminated, and neurological symptoms significantly improved. During the treatment, he experienced a one-degree rash, leukopenia, thrombocytopenia, and fatigue. This patient has been alive and well with disease control for 28 months since the diagnosis of meningeal metastases. Combining double-dose osimertinib and an intrathecal injection of pemetrexed demonstrated therapeutic efficacy and manageable adverse effects in this patient with advanced NSCLC with EGFR-mutant and LM.

Pembrolizumab combined with anlotinib improves therapeutic efficacy in pulmonary sarcomatoid carcinoma with TMB-H and PD-L1 expression: a case report and literature review.

Background: Pulmonary sarcomatoid carcinoma (PSC) is a unique subtype of non-small cell lung cancer (NSCLC) with a high degree of malignancy and poor therapeutic effects. With the widespread use of immune checkpoint inhibitors (ICIs) in recent years, few studies have reported that immunotherapy is effective against PSC. As a multi-target anti-vascular targeting agent, anlotinib showed a better anti-tumor effect in various cancer species. The paper reported the therapeutic and side effects of pembrolizumab combined with anlotinib in a patient with advanced PSC. Case presentation: This is a 73 year old female patient who underwent thoracoscopy right upper lobectomy and was diagnosed as locally advanced PSC. However, the patient experienced tumor recurrence and metastasis 7 weeks after surgery and was unable to tolerate chemoradiotherapy. Moreover, she detected TP53 mutation and found that tumor mutation burden (TMB) and PD-L1 were high expression. Therefore, the patient received pembrolizumab combined with anlotinib treatment. After 15 cycles of treatment, the tumor significantly shrank with no tumor activity. The evaluation of tumor efficacy is partial response (PR). During the treatment period, she experienced one-degree thyroid-stimulating hormone elevation and two-degree hand-foot syndrome. Pembrolizumab and anlotinib was continued for two years as a maintenance treatment. The patient had a good quality of life and no disease progression was observed. Currently, the patient is still alive without tumor progression and has overall survival exceeding 45 months and toxic side effects were tolerable. Conclusions: Combining ICIs and anti-angiogenic targeted therapy has brought new hope in treating advanced PSC. Additionally, TMB and PD-L1 expression could be potential predictive biomarkers of the efficacy in advanced PSC with immunotherapy.

High expression of MORC2 predicts worse neoadjuvant chemotherapy efficacy in triple negative breast cancer.

Tumor infiltrating lymphocytes (TILs) are closely related to the patients' prognosis. Recently, Microrchidia 2 (MORC2) has been documented as a prognostic and predictive biomarker in triple negative breast cancer (TNBC). To compare whether MORC2 is a better predictor than TILs, as well as clinicopathological parameters, in predicting the efficacy of neoadjuvant chemotherapy (NAC) in TNBC, we detected the expression of MORC2 on neoplastic cells through immunohistochemistry and quantified the stromal TILs through Hematoxylin-eosin staining on core biopsies from 50 locally advanced TNBC patients who underwent standard NAC. Among all the 50 patients, 28 (56%) cases had residual tumors, while the other 22 (44%) achieved pathologic complete response (pCR). In these studied patients, age and T-stage showed no correlation with pCR rate, while percentage of TILs, nodal involvement and expression of MORC2 on tumor cells showed significant association with pCR rate. Positive nodal involvement was correlation with worse pathologic response at multivariate analysis (P = .0036), and high TILs levels (≥50%) was positively associated with better NAC efficacy at univariate analysis (P = .002). Whereas high expression of MORC2 was statistically associated with worse pCR rate both at univariate (P < .001) and multivariate (P = .036) analysis. Our results indicate that MORC2 expression has a better predictive role in predicting the efficacy of NAC than TILs in TNBC patients.

LncRNA MIR4435-2HG mediates cisplatin resistance in HCT116 cells by regulating Nrf2 and HO-1.

PURPOSE: Cisplatin resistance is still a serious problem in the clinic. However, the underlying mechanism remains unknown. In our study, we investigated cisplatin resistance by using the cisplatin-resistant cell line HCT116R. METHODS: The HCT116 cell line, a colon cancer cell line, was purchased. Cell viability was determined using CCK-8 Assay Kit. The gene expression levels of MIR4435-2HG, Nrf2, and HO-1, and caspase activity were determined using qRT-PCR and Caspase 3 Assay Kit, respectively. RESULTS: In this study, we found that the levels of the lncRNA MIR4435-2HG were dramatically increased in the cisplatin-resistant cell line HCT116R. Knockdown of MIR4435-2HG in HCT116R cells significantly restored the sensitivity to cisplatin, inhibited cell proliferation and promoted cell apoptosis. Furthermore, Nrf2 and HO-1 mRNA levels, as critical molecules in the oxidative stress pathway, were inhibited by siRNAs targeting MIR4435-2HG, suggesting that MIR4435-2HG-mediated cisplatin resistance occurs through the Nrf2/HO-1 pathway. CONCLUSION: Our findings demonstrate that the lncRNA MIR4435-2HG is a main factor driving the cisplatin resistance of HCT116 cells.