Background: There is no standard management for small cell esophageal carcinoma (SCEC). The purpose of this multicenter, retrospective study (ChiSCER) was to investigate the treatment, outcomes, and risk factors impacting on survival endpoints in patients with limited-stage SCEC (LS-SCEC). Materials and Methods: Consecutive patients with LS-SCEC from 14 institutions between 2000 to 2020 in China were enrolled. Survival curves were constructed using the Kaplan-Meier method and compared by log-rank test. Univariate and multivariate Cox regression models and propensity score matching (PSM) analysis were adopted in prognostic analysis. Results were reported as hazard ratio (HR), 95% confidence interval (CI), and P value. Statistical significance was set as P value<0.05 in a two-tailed test. Results: Among 458 LS-SCEC patients, the median age was 63 (interquartile range [IQR], 57-68) years, 318 (69%) were males. Eighty-four (18%), 167 (36%), and 207 (45%) patients received chemotherapy (CT) alone, CT plus definitive radiotherapy (CT+RT), and CT plus radical surgery (CT+S), respectively. With a median follow-up time of 58.7 (95% CI, 48.9-68.6) months, the median OS and 3-year OS rate for all patients 24.3 (95% CI, 21.6-27) months and 37.3% (95% CI, 32.8%-42.5%), respectively. Multivariate analysis indicated that treatment modes, Karnofsky performance status (KPS), TNM stage, and CT cycle were independent prognostic factors for overall survival (OS) (P<0.05). Compared with CT alone, patients treated with CT+RT (HR, 0.57, 95% CI, 0.41-0.8, P=0.001) or CT+S (HR, 0.59, 95% CI, 0.42-0.82, P=0.002) had an improved OS, with no significant survival differences between CT+S and CT+RT groups after multivariate and PSM analyses (P>0.05). Subgroup analysis indicated that compared with CT+RT, patients with tumor location at lower 1/3 (HR, 0.59, 95% CI, 0.37-0.93, P=0.03) or tumor length>5 cm (HR 0.52, 95% CI, 0.3-0.9, P=0.02) could obtain significant OS benefit from CT+S. Patients with tumor location at middle 1/3 (HR 1.55, 95% CI, 1.03-2.36, P=0.04) or tumor length≤5 cm (HR 1.49, 95% CI, 1.02-2.17, P=0.04) favored CT+RT. Distant metastasis accounted for 73.7% of all treatment failures after multidisciplinary treatments. Conclusion: Surgery and RT were equally effective local therapies for patients with LS-SCEC. The personalized decision of local therapy should be made after comprehensive considerations on tumor location, length, comorbidities, and organ preservation.

Spiradenocarcinoma, or malignant eccrine spiradenoma (MES), is a rare sweat gland tumor originating from eccrine sweat glands. To the best of our knowledge, only two cases of MES of the external auditory canal have been reported to date. Here, we report a third case of MES located in the external auditory canal.

The N 6 ‐methyladenosine (m 6 A) modification is one of the most prevalent methylations in eukaryotic messenger RNA (mRNA), and it is essential for the development of many important biological processes such as multiple types of tumors. One of the most important enzymes catalyzing generation of m 6 A on mRNA is Wilms' tumor 1‐associating protein (WTAP); however, the potential role of WTAP in endometrial cancer (EC) still remains unknown. Here, we investigated WTAP expression level in cancer tissue and paracancerous tissue from an EC patient. Subsequently, WTAP was knocked down by small interfering RNA in EC cell line of Ishikawa and HEC‐1A, respectively. Cell proliferation, migration, and invasion were studied. The expression of caveolin‐1 (CAV‐1) was detected by quantitative polymerase chain reaction (qPCR). The enrichments of m 6 A and METTL3 on CAV‐1 were detected using RNA immunoprecipitation‐qPCR. The activity of nuclear factor‐κB (NF‐κB) was studied using Western blot. We observed that WTAP was dramatically upregulated in the cancer tissue, and there was an enhancement in cell proliferation, migration, and invasion and a decrease in EC apoptosis in vivo and in vitro, which indicated higher tumor malignancy and worse survival outcome. After WTAP was knocked down in EC cells, CAV‐1 was significantly upregulated and the enrichments of m 6 A and METTL3 at 3′‐untranslated region (UTR) region of CAV‐1 were decreased. Moreover, the activity of NF‐κB signaling pathway was inhibited by its regulator CAV‐1. Taken together, we concluded that WTAP could methylate 3′‐UTR of CAV‐1 and downregulate CAV‐1 expression to activate NF‐κB signaling pathway in EC, which promoted EC progression.

Background During radiotherapy (RT) procedure of breast cancer, portions of the heart and lung will receive some radiation dose, which may result in acute and late toxicities. In the current study, we report the experience of our single institution with organs at risk (OARs)-sparing RT with deep inspiration breath hold (DIBH) using an Optical Surface Management System (OSMS) and compare the dosimetric parameters with that of free breathing (FB). Patients and Methods Forty-eight cases diagnosed as early stage left-sided breast cancer scheduled for postoperative RT were enrolled. The OSMS was used to monitor the breathing magnitude and track the real-time respiratory status, which can control a stable lung and heart volume during RT delivery under DIBH. We did the dosimetric analysis of the heart, left anterior descending (LAD) coronary artery, lungs, and contralateral breast under FB and DIBH plans. Results Compared with FB-volumetric-modulated arc therapy (FB-VMAT), DIBH-VMAT resulted in significantly changed volumes to the heart and lungs receiving irradiation dose. The average mean heart dose and average D2%, V-5, and V(10)showed significant differences between the DIBH and FB techniques. For the LAD coronary artery, we found significantly reduced average mean dose, D2%, and V(10)with DIBH. Similar results were also found in the lungs and contralateral breast. The use of flattening-filter-free decreased treatment time compared with the flat beam mode in our VMAT (p< 0.05). For the 48 patients, there were no significant differences in the lateral, longitudinal, and vertical directions between OSMS and cone beam CT. Conclusions DIBH-VMAT with OSMS is very feasible in daily practice with excellent patient compliance in our single-center experience. Note that OSMS is an effective tool that may allow easier-to-achieve precise positioning and better and shorter position-verify time. Meanwhile, compared with FB, DIBH was characterized by lower doses to OARs, which may reduce the probability of cardiac and pulmonary complications in the future.

N6-methyladenosine (m6A) RNA methylation, one of the common RNA modifications, has been determined to execute crucial functions in tumorigenesis and cancer development. The m6A "writers" including methyltransferase like 3 (METTL3), METTL14, and Wilms tumor 1-associated protein (WTAP) contribute to the m6A modification process initiation. However, the coordination of m6A methyltransferase complex is not fully understood in endometrioid epithelial ovarian cancer (EEOC). In this study, mRNA and protein levels of METTL3, METTL14, and WTAP were detected in 33 EEOC cases using quantitative polymerase chain reaction (qPCR), immunohistochemistry, and western blot analysis. The overall m6A methylation was detected by dot plot. The METTL3 expression and overall m6A level were elevated in EEOC tissues, while the expressions of METTL14 and WTAP have no significant difference in EEOC compared to the adjacent tissues. The expression of METTL3 was an independent factor that correlated with poor malignancy and survival of EEOC patients. Moreover, METTL3 knockdown in TOV-112D and CRL-11731D cells weakened the capability of cell proliferation and migration, and promoted cell apoptosis compared to negative control and cells with WTAP or METTL14 knockdown using CCK-8 assay, transwell assay, wound healing assay, and TUNEL assay. Furthermore, METTL3 knockdown also reduced m6A enrichment of the genes associated with ovarian cancer including EIF3C, AXL, CSF-1, FZD10 in TOV-112D, and CRL-11731D cells by RIP-qPCR assay. Taken together, the high expressed METTL3 indicated poor malignancy and survival of EEOC via modulating the aberrant m6A RNA methylation. METTL3-mediated m6A modification, independent of WTAP and METTL14, was considered as a novel mechanism underlying m6A modulation and a potential therapeutic target of EEOC.

Background: Uncommon epidermal growth factor receptor (EGFR) mutations are a heterogeneous population of molecular alterations, and clinical data on the outcomes of afatinib in patients with non-small cell lung cancer (NSCLC) harboring uncommon EGFR mutations are limited. The purpose of this pooled analysis was to investigate the clinicopathological features of uncommon EGFR mutations in patients and the treatment response and survival associated with afatinib treatment. Methods: We performed a literature search in the NCBI PubMed database to identify relevant articles and completed a pooled analysis based on 37 related published studies.The relationship between clinical characteristics, EGFR mutation type and treatment response were analyzed using univariate chi-square analysis, and survival analysis was performed using the Kaplan–Meier method. Results: A total of 57 patients were included in this pooled analysis. The objective response rate to treatment with afatinib was 46.4%, with a median PFS of 7.0 months.Patients with a single uncommon EGFR mutation are more likely than patients with multiple mutations to show a good tumor response after receiving afatinib (ORR: 57.9% vs 26.3%, HR: 0.260, 95% CI: 0.078-0.869, p=0.029). Similarly, patients with a single uncommon EGFR mutation had a longer PFS than patients with multiple mutations (mPFS: 10.0 months vs 3.6 months, HR: 2.906, 95% CI: 1.496-5.646, p=0.002). In addition, for patients with a good treatment response, the PFS was also longer (HR: 2.902, 95% CI: 1.522-5.533, p=0.001). Conclusions: For patients with uncommon mutations, the outcomes of afatinib is worse than that of patients with classic sensitive mutations but higher than that of EGFR wild-type patients. Uncommon EGFR mutations contain various subtypes, and different subtypes have different sensitivities to afatinib. Patients with a single rare mutation show better treatment responses to afatinib and better prognoses than patients with multiple mutations.