Clinical best practices in interdisciplinary management of human epidermal growth factor receptor 2 antibody-drug conjugates-induced interstitial lung disease/pneumonitis: An expert consensus in China.

Antibody-drug conjugates (ADCs) have demonstrated effectiveness in treating various cancers, particularly exhibiting specificity in targeting human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Recent advancements in phase 3 clinical trials have broadened current understanding of ADCs, especially trastuzumab deruxtecan, in treating other HER2-expressing malignancies. This expansion of knowledge has led to the US Food and Drug Administration's approval of trastuzumab deruxtecan for HER2-positive and HER2-low breast cancer, HER2-positive gastric cancer, and HER2-mutant nonsmall cell lung cancer. Concurrent with the increasing use of ADCs in oncology, there is growing concern among health care professionals regarding the rise in the incidence of interstitial lung disease or pneumonitis (ILD/p), which is associated with anti-HER2 ADC therapy. Studies on anti-HER2 ADCs have reported varying ILD/p mortality rates. Consequently, it is crucial to establish guidelines for the diagnosis and management of ILD/p in patients receiving anti-HER2 ADC therapy. To this end, a panel of Chinese experts was convened to formulate a strategic approach for the identification and management of ILD/p in patients treated with anti-HER2 ADC therapy. This report presents the expert panel's opinions and recommendations, which are intended to guide the management of ILD/p induced by anti-HER2 ADC therapy in clinical practice.

[Lung Squamous Cell Carcinoma with EML4-ALK Fusion and TP53 Co-mutation 
Treated with Ensartinib: A Case Report and Literature Review].

Lung squamous cell carcinoma (LSCC) accounts for approximately 30% of non-small cell lung cancer (NSCLC) cases and is the second most common histological type of lung cancer. Anaplastic lymphoma kinase (ALK)-positive NSCLC accounts for only 2%-5% of all NSCLC cases, and is almost exclusively detected in patients with lung adenocarcinoma. Thus, ALK testing is not routinely performed in the LSCC population, and the efficacy of such treatment for ALK-rearranged LSCC remains unknown. Echinoderm microtubule associated protein like 4 (EML4)-ALK (V1) and TP53 co-mutations were identified by next generation sequencing (NGS) in this patient with advanced LSCC. On December 3, 2020, Ensatinib was taken orally and the efficacy was evaluated as partial response (PR). The progression-free survival (PFS) was 19 months. When the disease progressed, the medication was changed to Loratinib. To our knowledge, Enshatinib created the longest PFS of ALK-mutant LSCC patients treated with targeted therapy since literature review. Herein, we described one case treated by Enshatinib involving a patient with both EML4-ALK and TP53 positive LSCC, and the relevant literatures were reviewed for discussing the treatment of this rare disease.
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Kirsten rat sarcoma viral oncogene homolog G12C mutant advanced non-small-cell lung cancer treated with MEK1/2 inhibitor trametinib: a case report.

No targeted therapies are approved for non-small-cell lung cancer (NSCLC) with Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation to date. Trametinib, a selective allosteric inhibitor of the MEK1/2, demonstrated debatable clinical activity in KRAS-mutant NSCLC. In this case, we present a recurrent advanced NSCLC with KRAS G12C mutation successfully treated with single-agent trametinib therapy. An 87-year-old man who underwent radiotherapy for the right lung adenocarcinoma was admitted to clinical oncology center for recurrent lesions in bilateral lungs. He was unwilling to perform second-line chemotherapy, but underwent molecular profiling and revealed the KRAS G12C mutation. The single-agent target therapy of trametinib showed clinical benefit without obvious toxicity. Furthermore, this report reviewed the previous date of the preclinical and clinical and summarized that KRAS G12C mutation may be more sensitive to the inhibition of mitogen-activated protein kinase kinase. This case advocates for routine screening of KRAS point mutations in the utility of precision medicine and suggests that treatment with trametinib in advanced NSCLC cases with KRAS G12C mutation is well tolerated and effective, especially for those very elderly or unsuitable for more aggressive chemotherapy.

Triple administration of osimertinib followed by chemotherapy for advanced lung adenocarcinoma: A case report.

BACKGROUND: Osimertinib is the recommended first-line treatment for adult patients with epidermal growth factor receptor (EGFR) mutation positive advanced or metastatic non-small cell lung cancer (NSCLC). However, primary or acquired resistance to EGFR-tyrosine kinase inhibitors (EGFR-TKIs) seems inevitable, and when drug-resistance occurs during treatment with osimertinib, the standard of care is to discontinue the TKI. CASE SUMMARY: A 57-year-old female patient with lung adenocarcinoma presented with an irritating cough accompanied by chest distress of one month duration. An enhanced head magnetic resonance imaging scan showed brain metastases. An EGFR mutation (exon 21 L858R) was detected in pleural fluid. The patient was treated with oral osimertinib (80 mg once daily) from January 2018 but developed progressive disease on December 2018. She was then successfully treated with re-challenge and tri-challenge with osimertinib (80 mg once daily) by resensitization chemotherapy twice after the occurrence of drug-resistance to osimertinib, and to date has survived for 31 mo. CONCLUSION: This case may provide some selective therapeutic options for NSCLC patients with acquired drug-resistance who were previously controlled on osimertinib treatment.

Association between clinicopathological features and prognosis significance of PD-L1 expression in small cell lung cancer patients: a systemic review and meta-analysis.

BACKGROUND: Programmed death ligand-1 (PD-L1) has been identified as an established biomarker for predicting response to immunotherapy in a variety types of cancer. However, the clinicopathological and prognostic significance of this protein in small cell lung cancer (SCLC) patients remains controversial. METHODS: Eligible studies extracted from the databases of PubMed, MEDLINE, Embase, and CNKI databases were evaluated. Statistical analysis was performed using STATA 11.2 software. RESULTS: A total of 483 PD-L1+ cases and 570 controls from 11 publications were extracted. Either overall analysis or subcategory analysis showed that no significant association between higher PD-L1 expression and gender (n=8, OR 1.08, 95% CI: 0.73-1.61, P=0.704, I2=0.0%), tumor stage (n=5, OR 0.71, 95% CI: 0.20-2.56, P=0.599, I2=86.5%), smoking status (n=4, OR 0.85, 95% CI: 0.41-1.73, P=0.646, I2=0.0%), and the level of serum lactate dehydrogenase (LDH) (n=4, OR 0.76, 95% CI: 0.48-1.20, P=0.241, I2= 21.6%). PD-L1 expression had no positive correlation with overall survival (OS) (n=11, HR 0.97, 95% CI: 0.61-1.56, P=0.904, I2= 83.2%) in overall analysis. However, the stratified analysis showed that increased expression of PD-L1 predicted a significantly better OS in monoclonal antibody (mAb) subgroup and Food and Drug Administration (FDA) approved antibody clone specification (22C3/28-8/SP142/SP263) subgroup without significant heterogeneity. CONCLUSIONS: PD-L1 is not an important predictor of most clinicopathological features of SCLC patients, but it can predict an improved survival when using mAb or FDA approved clone specifications in IHC assays.

Nonsmall cell lung cancer with rare exon 7 p.A289V mutation in the EGFR gene responds to Icotinib treatment: A case report.

RATIONALE: Mutation p.A289V involving extracellular region of epidermal growth factor receptor (EGFR) exon 7 has not yet been reported in nonsmall cell lung cancer (NSCLC). Studies have shown p.A289V mutation responding to tyrosine kinase inhibitors (TKIs) in glioblastoma cell lines suggesting the point mutation as a potential therapeutic target. However, sufficient evidence of the effect of TKI treatment on the p.A289V mutation involved in NSCLC is not available. PATIENT CONCERNS: An 80-year-old nonsmoker male with lung mass was suffering from severe bone pain. DIAGNOSIS: Needle biopsy and positron emitted tomography/computed tomography were performed. The patient was diagnosed with advanced NSCLC adenocarcinoma with bone and lymphatic metastasis. Next-generation sequencing of circulating tumor DNA was performed, which identified a p.A289V mutation in the EGFR gene of the patient. INTERVENTIONS: Our patient refused to receive chemotherapy and tried Icotinib treatment. OUTCOMES: Our patient had a partial response to Icotinib after treatment for 5 months during the therapeutic trial by TKIs. The patient showed adverse symptoms of mild diarrhea and rash (Common Terminology Criteria for Adverse Events grade 1) during the treatment. LESSONS: In this case, Icotinib prevented completion of the signal transduction cascade of p.A289V mutant in NSCLC. Our finding may expand the EGFR mutation spectrum for TKI treatment in NSCLC. However, the finding needs to be confirmed at a larger scale with NSCLC in Chinese and other populations.

Successful management of rare gingival metastasis from gastric adenocarcinoma: a case report and literature review.

BACKGROUND: Gastric cancer rarely metastasizes to the oral cavity, especially to gingiva. Only 18 cases have been reported worldwide to date. This paper herein presents the nineteenth case of gingival metastasis from gastric cancer. CASE PRESENTATION: A 75-year-old man who underwent a radical gastrectomy for gastric adenocarcinoma was admitted to clinical oncology center for gingival mass which was originally diagnosed as epulis. The subsequent positron emission tomography-computed tomography (PET-CT) and histopathological examination revealed a gingival metastatic adenocarcinoma originated from gastric carcinoma. Then three-dimensional conformal radiotherapy (3D-CRT) with synchronization and sequential chemotherapy demonstrated clinical benefit in this patient. Furthermore, this research reviewed the records of 18 cases of gingival metastasis from gastric carcinoma in English, Japanese, and Chinese literature, and summarized the clinicopathologic features of the disease based on previously published papers. CONCLUSION: This case suggests that gingival metastasis from gastric cancer is worthy of vigilance. Biopsy and immunohistochemical (IHC) staining should be used for the final diagnosis. Moreover, the patient with uncommon gingival metastatic lesion can be successfully treated by radiotherapy with adjuvant chemotherapy.

Nestin Expression Is Associated with Poor Clinicopathological Features and Prognosis in Glioma Patients: an Association Study and Meta-analysis.

Nestin has been identified as a molecular marker of neural progenitor cells and putative glioma stem cells (GSCs). Various studies examining the relationship between nestin expression with the clinical outcome in glioma patients have yielded inconclusive results. Thus, we conducted a systematic review to evaluate the association of nestin with prognosis and clinicopathological features of glioma patients. The electronic searches were performed through the database of PubMed, MEDLINE, Embase, and CNKI. In total, this meta-analysis included 14 studies covering 897 nestin + cases and 704 controls. The correlation between nestin expression and clinicopathological or prognostic parameters was evaluated by Stata 11.0 software. Our results showed that nestin protein abundance was significantly correlated with the histological grade [odds ratio (OR) = 4.36, 95 % confidence interval (CI) = 2.14-8.88, P = 0.003] of glioma. With respect to prognosis, nestin expression was positively correlated with overall survival (OS) [hazard ratio (HR) = 1.98, 95 % CI = 1.30-3.02, P = 0.000] and progression-free survival (PFS) (HR = 1.90, 95 % CI = 1.18-3.07, P = 0.040). The further stratified analysis not only defined the predictive function of nestin in different ages but also revealed that different antibodies did not alter the positive outcomes and higher standard cutoff values were more suitable for the accurate assay of nestin. Taken together, our results indicate that nestin may play an important role in the prediction of the clinicopathology and poor prognosis of glioma patients. This study should be taken into consideration in the development of new diagnostic and therapeutic programs.

Three-dimensional cell culture: A powerful tool in tumor research and drug discovery.

In previous years, three-dimensional (3D) cell culture technology has become a focus of research in tumor cell biology, using a variety of methods and materials to mimic the in vivo microenvironment of cultured tumor cells ex vivo. These 3D tumor cells have demonstrated numerous different characteristics compared with traditional two-dimensional (2D) culture. 3D cell culture provides a useful platform for further identifying the biological characteristics of tumor cells, particularly in the drug sensitivity area of the key points of translational medicine. It promises to be a bridge between traditional 2D culture and animal experiments, and is of great importance for further research in the field of tumor biology. In the present review, previous 3D cell culture applications, focusing on anti-tumor drug susceptibility testing, are summarized.

A three-dimensional collagen scaffold cell culture system for screening anti-glioma therapeutics.

Three-dimensional (3D) culture, which can simulate in vivo microenvironments, has been increasingly used to study tumor cell biology. Since most preclinical anti-glioma drug tests still rely on conventional 2D cell culture, we established a collagen scaffold for 3D glioma cell culture. Glioma cells cultured on these 3D scaffolds showed greater degree of dedifferentiation and quiescence than cells in 2D culture. 3D-cultured cells also exhibited enhanced resistance to chemotherapeutic alkylating agents, with a much higher proportion of glioma stem cells and upregulation of O6-methylguanine DNA methyltransferase (MGMT). Importantly, tumor cells in 3D culture showed chemotherapy resistance patterns similar to those observed in glioma patients. Our results suggest that 3D collagen scaffolds are promising in vitro research platforms for screening new anti-glioma therapeutics.

Optimized dissociation protocol for isolating human glioma stem cells from tumorspheres via fluorescence-activated cell sorting.

Fluorescence-activated cell sorting (FACS) based on the surface marker CD133 is the most common method for isolating glioma stem cells (GSCs) from heterogeneous glioma cell populations. Optimization of this method will have profound implications for the future of GSC research. Five commonly used digestion reagents, Liberase-TL, trypsin, TrypLE, Accutase, and non-enzymatic cell dissociation solution (NECDS), were used to dissociate glioma tumorspheres derived from two primary glioma specimens (091214 and 090116) and the cell lines U87 and T98G. The dissociation time, cell viability, retention of CD133, and stemness capacity were assessed. The results showed that single cells derived from the Liberase-TL (200 µg/ml) group exhibited high viability and less damage to the antigen CD133. However, the efficiency of NECDS for dissociating the tumorspheres into single cells was fairly low. Meanwhile, the use of this digestion reagent resulted in obvious cellular and antigenic impairments. Taken together, Liberase-TL (200 µg/ml) is an ideal reagent for isolating GSCs from tumorspheres. In contrast, the use of NECDS for such a protocol should be carefully considered.

Iris metastasis from esophageal squamous cell carcinoma: A case report.

Carcinoma metastatic to the eye is a rare condition, typically associated with a poor prognosis. Breast and lung cancers are the most common sources of intraocular metastases, and the majority of metastatic lesions involve the posterior uvea, with <8% of reported cases arising in the iris. Intraocular metastasis as the presenting form of esophageal carcinoma is highly uncommon. In the present report, a rare case of metastatic iris tumor resulting from esophageal squamous cell carcinoma is discussed. A 64-year-old patient presented with a progressively distending pain in the right eye, with associated blurred vision. Local and systemic evaluation was performed, followed by treatment. Multiple examinations identified a neoplasm in the right iris and postoperative pathology revealed that the iris lesion was a metastasis of esophageal squamous cell cancer origin. The patient was treated with adjuvant radiation. To the best of our knowledge, this was only the second reported case of esophageal squamous cell carcinoma metastasizing to the iris.

ALDH1A1 expression correlates with clinicopathologic features and poor prognosis of breast cancer patients: a systematic review and meta-analysis.

BACKGROUND: Aldehyde dehydrogenase 1 family member A1 (ALDH1A1) has been identified as a putative cancer stem cell (CSC) marker in breast cancer. However, the clinicopathological and prognostic significance of this protein in breast cancer patients remains controversial. METHODS: This meta-analysis was conducted to address the above issues using 15 publications covering 921 ALDH1A1(+) cases and 2353 controls. The overall and subcategory analyses were performed to detect the association between ALDH1A1 expression and clinicopathological/prognostic parameters in breast cancer patients. RESULTS: The overall analysis showed that higher expression of ALDH1A1 is associated with larger tumor size, higher histological grade, greater possibility of lymph node metastasis (LNM), higher level expression of epidermal growth factor receptor 2 (HER2), and lower level expression of estrogen receptor (ER)/progesterone receptor (PR). The prognosis of breast cancer patients with ALDH1A1(+) tumors was poorer than that of the ALDH1A1(-) patients. Although the relationships between ALDH1A1 expression and some clinicopathological parameters (tumor size, LNM, and the expression of HER2) was not definitive to some degree when we performed a subcategory analysis, the predictive values of ALDH1A1 expression for histological grade and survival of breast cancer patients were significant regardless of the different cutoff values of ALDH1A1 expression, the different districts where the patients were located, the different clinical stages of the patients, the difference in antibodies used in the studies, and the surgery status. CONCLUSIONS: Our results indicate that ALDH1A1 is a biomarker to predict tumor progression and poor survival of breast cancer patients. This marker should be taken into consideration in the development of new diagnostic and therapeutic program for breast cancer.

Related risk factors for injury severity of e-bike and bicycle crashes in Hefei.

OBJECTIVE: To explore the related risk factors of injuries caused by e-bike and bicycle crashes in Hefei, Anhui. METHODS: Between June 2009 and June 2011, the records of injuries were triggered by e-bike and bicycle crashes in Hefei maintained by 105th Hospital of PLA. A form was designed to document patient age, gender, road user category (driver, passenger, pedestrian), safety factors (safety devices present, speed, traffic violations), environmental factors (time of trauma, light conditions, road surface), crash mode, impact type, and vehicle type. RESULTS: Of the 205 cases, 108 were female and 97 were male. One hundred forty-six patients suffered injuries due to e-bike accidents and 59 due to bicycle accident. The chi-squared test compared distribution of categorical variables suggested that age (P =.0250), road user category (P =.0278), traffic rule violations (P =.0132), crash mode (P =.0027), impact type (P =.0019), and vehicle type (P =.0219) are related to the severity of injuries caused by e-bike/bicycle crashes in Hefei. The multiple-factor nonconditional logistic regression analysis showed that injury severity is the most commonly sustained within the vehicle type (odds ratio [OR] = 14.418; 95% confidence interval [CI], 4.680-44.418), followed by crash mode (OR = 11.556; 95% CI, 4.430-30.142), traffic rule violations (OR = 4.735; 95% CI, 1.934-11.594), and age (OR = 2.910; 95% CI, 1.213-6.979). CONCLUSIONS: With the study of e-bike/bicycle crashes in Hefei, primary identification of the risk factors for the traffic injuries is obtained. These findings are important in decision making regarding preventive measures.