•Our series is one of the first and the largest assessing ICPi efficacy in LCNET.•In LCNET, ICPi outcomes are comparable to outcomes observed in NSCLC.•In LCNET, ORR with ICPi - 33 %, mPFS with ICPi ...- 4.2 months.•mOS with ICPi: 11.8 and 6.9 months in LCNET and NSCLC, respectively (p-0.23).•The correlation with LCNET molecular subtype needs further exploration.
Little is known regarding the ICPi efficacy in LCNEC. We explored the efficacy and safety of ICPi in LCNEC and assessed its impact on OS.
Thirty-seven consecutive patients with advanced LCNEC were selected from the Davidoff Cancer Center database. These were divided into groups A1 (patients treated with ICPi, n-23) and A2 (patients not treated with ICPi, n-14). Additionally, group A1* was introduced (patients treated with ICPi as a monotherapy, n-21). Another cohort of advanced non-LCNEC lung cancer patients treated with nivolumab at five Israeli cancer centers was chosen as a comparator (group B, n-270). ORR, PFS with ICPi in group A1* were assessed (RECIST 1.1), OS with ICPi was compared between groups A1* and B. OS since advanced disease diagnosis (OSDx) was compared between groups A1 and A2.
In group A1*, ORR and median PFS with ICPi were 33 %, and 4.2 months (95 % CI, 2.4–8.1), respectively. With median follow-up since start of ICPi of 6.2 months IQR 2.2–12.1 and 4.9 months IQR 2.3–8.9 in groups A1* and B, respectively, 52 % and 64 % of patients died in groups A1* and B, respectively. Median OS with ICPi comprised 11.8 months (95 % CI, 3.7-NR) and 6.9 months (95 % CI, 5.5–8.1) in groups A1* and B, respectively (p-0.23). Median OSDx was 14.5 months (95 % CI, 10.1–38.9) and 10.3 months (95 % CI, 2.6-NR), in groups A1 and A2, respectively (p-0.54).
In advanced LCNEC, ICPi outcomes are comparable to the outcomes observed in advanced NSCLC. Future research is needed to clarify the impact of ICPi on OS, and to correlate its benefit with tumor mutational landscape.
Lung cancer has the highest mortality rate among cancer patients in the world, in particular because most patients are only diagnosed at an advanced and noncurable stage. Computed tomography (CT) ...screening on high-risk individuals has shown that early detection could reduce the mortality rate. However, the still high false-positive rate of CT screening may harm healthy individuals because of unnecessary follow-up scans and invasive follow-up procedures. Alternatively, false-negative and indeterminate results may harm patients due to the delayed diagnosis and treatment of lung cancer. Noninvasive biomarkers, complementary to CT screening, could lower the false-positive and false-negative rate of CT screening at baseline and thereby reduce the number of patients that need follow-up and diagnose patients at an earlier stage of lung cancer. Lung cancer tissue generates lung cancer-associated proteins to which the immune system might produce high-affinity autoantibodies. This autoantibody response to tumor-associated antigens starts during early stage lung cancer and may endure over years. Identification of tumor-associated antigens or the corresponding autoantibodies in body fluids as potential noninvasive biomarkers could thus be an effective approach for early detection and monitoring of lung cancer. We provide an overview of differentially expressed protein, antigen, and autoantibody biomarkers that combined with CT imaging might be of clinical use for early detection of lung cancer.
Vulvar high-grade neuroendocrine carcinomas (HGNECs) are rare and primarily thought to represent Merkel cell carcinoma (MCC). We present the clinicopathologic features of 16 such cases, the largest ...series to date. Patients were most often White, postmenopausal, and symptomatic from a palpable vulvar mass/nodule. Tumors ranged from 0.7 to 6 cm and most commonly involved the labium majus. Majority of the cases were pure HGNECs (15/16) with small cell (SC) morphology (14/16); 2 were large cell neuroendocrine carcinomas, of which 1 was combined with moderately differentiated adenocarcinoma. All tumors expressed synaptophysin. Of the 14 HGNECs with SC morphology, 6 were CK20-positive MCCs with characteristic CAM5.2 and neurofilament (NF) expression. Five of these MCCs were positive for Merkel cell polyoma virus large T-antigen (MCPyVLTAg). In contrast, 6 HGNECs with SC morphology were negative for CK20, NF, and MCPyVLTAg and classified as SCNECs. High-risk human papilloma virus was positive in all SCNECs and negative in all MCCs. One case of HGNEC with SC morphology could not be entirely characterized due to lack of tissue for ancillary testing. Five of 12 (42%) cases had a discrepant diagnosis initially rendered. Most patients (10/15) presented with International Federation of Gynecology and Obstetrics stage III or IV disease. Usual sites of metastasis included inguinal lymph node, liver, bone, and lung. Twelve patients underwent surgery with adjuvant chemotherapy and/or radiation therapy, 1 received adjuvant immunotherapy, and 1 patient received neoadjuvant chemotherapy followed by surgery and adjuvant radiation therapy. Median overall survival was 24 months (range: 7 to 103 mo), and overall 5-year survival was 12% (95% confidence interval: 1% to 39%). In summary, vulvar HGNECs are rare, aggressive neoplasms that can be further subclassified into MCC, SCNEC, and large cell neuroendocrine carcinoma. CK20, CAM5.2, NF, TTF-1, MCPyVLTAg, and high-risk human papilloma virus facilitate the distinction of MCC from SCNEC. Proper identification of vulvar HGNECs is critical for patient management.
Cancer statistics: Breast cancer in situ Ward, Elizabeth M.; DeSantis, Carol E.; Lin, Chun Chieh ...
CA: a cancer journal for clinicians,
November/December 2015, Letnik:
65, Številka:
6
Journal Article
During the past few decades, the incidence of thyroid cancer has increased substantially in many countries, including the USA. The rise in incidence seems to be attributable both to the growing use ...of diagnostic imaging and fine-needle aspiration biopsy, which has led to enhanced detection and diagnosis of subclinical thyroid cancers, and environmental factors. The latest American Thyroid Association (ATA) practice guidelines for the management of adult patients with thyroid nodules and differentiated thyroid cancer differ substantially from the previous ATA guidelines published in 2009. Specifically, the problems of overdiagnosis and overtreatment of a disease that is typically indolent, where treatment-related morbidity might not be justified by a survival benefit, now seem to be acknowledged. As few modifiable risk factors for thyroid cancer have been established, the specific environmental factors that have contributed to the rising incidence of thyroid cancer remain speculative. However, the findings of several large, well-designed epidemiological studies have provided new information about exposures (such as obesity) that might influence the development of thyroid cancer. In this Review, we describe the changing incidence of thyroid cancer, suggest potential explanations for these trends, emphasize the implications for patients and highlight ongoing and potential strategies to combat this growing clinical and public health issue.
•No associations between peritumoral edema and immunohistochemical features.•In NSCLC patients, an association between MMP9 expression and edema volume.•In NSCLC patients, an association between ...tumor volume and angiogenesis.
Perifocal edema of brain tumors is associated with survival and neurological symptoms. Our aim was to analyze associations between perifocal edema and immunohistochemical features including proliferation potential, microvessel density, neoangiogenesis and invasiveness in brain metastasis (BM).
35 patients with BM were included into the retrospective study. The tumors were localized supratentorial in 25 lesions (71.4%) and infratentorial in 10 lesions (28.6%). The following immunohistochemical features were calculated on histopathological specimens: microvessel density, proliferation index Ki 67, matrix-metallopeptidase 9 (MMP9) extracellular matrix metalloproteinase inducer (EMMPRIN) and vascular endothelial growth factor (VEGF) expression. Tumor and edema volumes were estimated semiautomatically on magnetic resonance images.
There were no correlations between tumor volume and edema volume. Moreover, no correlation was identified between the investigated immunohistochemical features and tumor/edema volume. In the non-small cell lung cancer subgroup, a positive correlation between tumor volume and VEGF expression was observed (r = 0.52, P = 0.02) and edema volume correlated inversely with MMP9 expression (r = −0.53, P = 0.02).
In BM, no linear associations exist between tumor volumes, edema volumes and immunohistochemical features reflecting proliferation potential, neoangiogenesis, microvessel density and MMP9 expression. However, in the subgroup of non-small cell lung cancer, there might be associations between MMP9 expression and edema volume as well as between tumor volume and angiogenesis.
Bladder cancer is the sixth most common cancer in humans. This heterogeneous set of lesions including urothelial carcinoma (Uca) and squamous cell carcinoma (SCC) arise from the urothelium, a ...stratified epithelium composed of K5-expressing basal cells, intermediate cells and umbrella cells. Superficial Uca lesions are morphologically distinct and exhibit different clinical behaviours: carcinoma in situ (CIS) is a flat aggressive lesion, whereas papillary carcinomas are generally low-grade and non-invasive. Whether these distinct characteristics reflect different cell types of origin is unknown. Here we show using lineage tracing in a murine model of carcinogenesis that intermediate cells give rise primarily to papillary lesions, whereas K5-basal cells are likely progenitors of CIS, muscle-invasive lesions and SCC depending on the genetic background. Our results provide a cellular and genetic basis for the diversity in bladder cancer lesions and provide a possible explanation for their clinical and morphological differences.
Recent advances in immunotherapy highlight the antitumor effects of immune checkpoint inhibition despite a relatively limited subset of patients receiving clinical benefit. The selective class I ...histone deacetylase inhibitor entinostat has been reported to have immunomodulatory activity including targeting of immune suppressor cells in the tumor microenvironment. Thus, we decided to assess whether entinostat could enhance anti-PD-1 treatment and investigate those alterations in the immunosuppressive tumor microenvironment that contribute to the combined antitumor activity.
We utilized syngeneic mouse models of lung (LLC) and renal cell (RENCA) carcinoma and assessed immune correlates, tumor growth, and survival following treatment with entinostat (5 or 10 mg/kg, p.o.) and a PD-1 inhibitor (10 and 20 mg/kg, s.c.).
Entinostat enhanced the antitumor effect of PD-1 inhibition in two syngeneic mouse tumor models by reducing tumor growth and increasing survival. Entinostat inhibited the immunosuppressive function of both polymorphonuclear (PMN)- and monocytic-myeloid derived suppressor cell (M-MDSC) populations. Analysis of MDSC response to entinostat revealed significantly reduced arginase-1, iNOS, and COX-2 levels, suggesting potential mechanisms for the altered function. We also observed significant alterations in cytokine/chemokine release in vivo with a shift toward a tumor-suppressive microenvironment.
Our results demonstrate that entinostat enhances the antitumor effect of PD-1 targeting through functional inhibition of MDSCs and a transition away from an immune-suppressive tumor microenvironment. These data provide a mechanistic rationale for the clinical testing and potential markers of response of this novel combination in solid tumor patients.
Salivary gland epithelial neoplasms are rare in children and adolescents, with only a handful of large series having been published. A retrospective study was conducted for 57 cases in patients 20 ...years or younger. The tumors were located in the parotid (n=36), submandibular gland (n=7), and minor salivary glands (n=14). Nineteen (33%) tumors were pleomorphic adenoma, whereas the remaining (67%) were malignant. The histologic types of carcinomas were mucoepidermoid carcinoma (MEC, n=19, 33%), acinic cell carcinoma (n=7, 12%), adenoid cystic carcinoma (n=6, 11%), secretory carcinoma (mammary analogue) (SC, n=4, 7%), and myoepithelial carcinoma (n=2, 4%). Ninety-three percent (13/14) of the minor and 58% (25/43) of the major salivary gland tumors were malignant. A 7-year-old girl (2%) with a high-grade MEC died from her disease because of uncontrollable locoregional recurrence. Seven patients (16%) developed recurrence including 2 distant metastases from adenoid cystic carcinoma and 6 locoregional recurrences (2 pleomorphic adenomas, 1 SC, 1 myoepithelial carcinoma, 1 adenoid cystic carcinoma, and 1 MEC). The following parameters were associated with decreased disease-free survival in malignant tumors: elevated mitotic index of >4/10 high-power fields (log-rank test, P<.001), and advanced American Joint Committee on Cancer pT (P=.029) and pN stage (P<.001). In conclusion, myoepithelial carcinoma and SC can occur in the pediatric population and should be considered in the differential diagnosis. Salivary gland malignancies in children appear to have better clinical outcome, associated with a 10-year recurrence-free survival rate of 74% and a 10-year disease-specific survival of 94%.
•Two-thirds of pediatric salivary gland tumors are malignant, with MEC being the most common tumor.•Myoepithelial carcinoma and SC can occur in the pediatric population.•Salivary gland malignancies in children appear to have better clinical outcome.
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