Appearance Of Distant Metastases Research Articles

[Translated article] Longitudinal Study of Different Progression Patterns in High-Risk Cutaneous Squamous Cell Carcinoma

Background and objectiveCutaneous squamous cell carcinoma (cSCC) is the second leading cause of skin cancer mortality in Europe. Few studies have analyzed the different pathways of this tumor progression in its natural history. The main objective of this study was to analyze the different metastatic and progression pathways and their temporal occurrence in the evolution of cSCC. Material and methodWe conducted a multicenter, retrospective, and observational study of consecutive high-risk sSCCs included in the SQUAMATA project. ResultsA total of 222 out of the 1346 patients included relapsed. The most frequent route of progression was the lymphatic one (62.6%). A total of 20.2% of the cases with lymphatic progression developed distant metastases. Only 1 case (3.1%) of distant metastasis followed local recurrence without previous lymphatic metastasis. The median time to disease-related mortality was longer in patients who developed systemic metastases than in those who died of locoregional progression. ConclusionsThe mortality of patients with cSCC is mostly due to the regional progression of their lymphatic metastases. The appearance of distant metastases is practically always (96.9%) associated with previous lymphatic metastatic progression. Therefore, in the future, new studies will be needed to assess the regional management of cSCC in both surgical and adjuvant therapies.

Estudio longitudinal de los diferentes patrones de progresión en el carcinoma cutáneo de células escamosas de alto riesgo

Background and objectiveCutaneous squamous cell carcinoma (cSCC) is the second leading cause of skin cancer mortality in Europe. Few studies have analyzed the different pathways of this tumor progression in its natural history. The main objective of this study was to analyze the different metastatic and progression pathways and their temporal occurrence in the evolution of cSCC. Material and methodWe conducted a multicenter, retrospective, and observational study of consecutive high-risk sSCCs included in the SQUAMATA project. ResultsA total of 222 out of the 1346 patients included relapsed. The most frequent route of progression was the lymphatic one (62.6%). A total of 20.2% of the cases with lymphatic progression developed distant metastases. Only 1 case (3.1%) of distant metastasis followed local recurrence without previous lymphatic metastasis. The median time to disease-related mortality was longer in patients who developed systemic metastases than in those who died of locoregional progression. ConclusionsThe mortality of patients with cSCC is mostly due to the regional progression of their lymphatic metastases. The appearance of distant metastases is practically always (96.9%) associated with previous lymphatic metastatic progression. Therefore, in the future, new studies will be needed to assess the regional management of cSCC in both surgical and adjuvant therapies.

Efficacy and safety of the combination of cisplatin plus nab-paclitaxel and nivolumab with radiotherapy after maximal tumor resection in non-metastatic muscle invasive bladder cancer (CNN-BC trial).

TPS723 Background: The therapeutic gold standard for muscle invasive bladder cancer (MIBC) is radical cystectomy (RC) preceded by neoadjuvant chemotherapy when appropriate. However, RC is a major surgery procedure with 13% rate of severe complication and a perioperative mortality rate of about 1.5 - 5 %. Trimodal therapy (TMT) is a “bladder sparing” option alternative to RC. TMT consists of complete transurethral bladder tumor resection (TURBT) followed by a combination of systemic chemotherapy and locoregional radiotherapy (RT), with the option of “salvage” cystectomy in case of local treatment failure. Immunotherapy with anti-PD1/PD-L1 monoclonal antibody significantly improves survival of metastatic BC patients, and it seems to potentiate the activity of RT without increased toxicity. Therefore, we investigate the role of a multimodal TMT strategy to increase the disease-free survival (DFS) and avoid or delay RC in non-metastatic MIBC pts. Methods: CNN-BC trial (NCT05203913) is a phase 2, open-label, mono-institutional study evaluating the activity and safety of TMT with cisplatin, nab-paclitaxel and nivolumab as systemic therapy in non-metastatic MIBC pts. Eligible pts should have undergone complete TURBT with diagnosis of T2-T3 N0M0 urothelial carcinoma, and no evidence of lymph nodes or metastatic disease at FDG-PET within 6 weeks from the start of treatments. TMT consists of nivolumab (480 mg IV every 4 weeks for a total of 13 doses), weekly nab-paclitaxel (60mg/m2) plus cisplatin (20mg/m2) administered concurrently with RT (60Gy in 25 fractions over 5 weeks on original bladder tumor, plus a concomitant boost of 50Gy in 25 fractions on whole bladder and pelvic nodes). The primary endpoint is the 1-year DFS rate, defined as the rate of survival free of recurrence in pelvic nodes or bladder, or appearance of distant metastases. Secondary endpoints include: the rate of pts who require salvage cystectomy, the rate of locoregional complete response (CR) and of locoregional DFS, median DFS, safety, and quality of life. Exploratory biomarkers analysis will be performed. The trial is actively recruiting. Clinical trial information: NCT05203913 .

Solitary fibrous tumor: features of the clinical course, radiation and laboratory diagnostics, therapy: A review

Solitary fibrous tumor (SFT) is a relatively rare mesenchymal neoplasm, mainly affecting serous membranes and soft tissues.It is distinguished by a long-term course, a variable risk of metastasis, the possibility of occurrence in any anatomical region, as well as a low-specific histological structure.Moreover, the last two features of SFT are the main causes of diagnostic errors in morphological verification of a neoplasm. Despite the fact that in the twentieth century SFT was mentioned in the scientific literature quite rarely and, as a rule, in the form of single observations, in the last two decades, due to the widespread use of new molecular genetic research methods and the identification of specific mutations in mesenchymal tumors, the quality and accuracy have significantly increased. making a diagnosis. In addition, the clinical observations accumulated in recent decades in a considerable number of cases made it possible to assess in more detail the clinical and morphological parameters of the SFT associated with the risk of local recurrence and the appearance of distant metastases. This article analyzes the modern literature on epidemiology, molecular pathology, features of radiation and morphological diagnostics, aspects of the genesis of solitary fibrous tumor, as well as the choice of optimal treatment for patients.

Radiomics Predicts for Distant Metastasis in Locally Advanced Human Papillomavirus-Positive Oropharyngeal Squamous Cell Carcinoma.

Simple SummaryThere is strong evidence that locally advanced human papillomavirus positive (HPV+) oropharyngeal squamous cell carcinoma (OPSCC) carries a significantly better prognosis than HPV negative OPSCC, suggesting the possibility of treatment de-escalation and, therefore, toxicity reduction in this patient population. The lack of success in clinical trials towards this end presses the need to risk stratify locally advanced HPV+ OPSCC patients who can safely have treatment de-escalated. The present study had recourse to radiomics for this purpose and showed that radiomics has the ability to discriminate patients with locally advanced HPV+ OPSCC who went on to develop distant metastasis after completion of definitive chemoradiation or radiation alone. The implications of this study aid in demonstrating the potential pivotal role of radiomics in predictive risk assessment and personalizing therapy for this patient population.(1) Background and purpose: clinical trials have unsuccessfully tried to de-escalate treatment in locally advanced human papillomavirus positive (HPV+) oropharyngeal squamous cell carcinoma (OPSCC) with the goal of reducing treatment toxicity. The aim of this study was to explore the role of radiomics for risk stratification in this patient population to guide treatment. (2) Methods: the study population consisted of 225 patients with locally advanced HPV+ OPSCC treated with curative-intent radiation or chemoradiation therapy. Appearance of distant metastasis was used as the endpoint event. Radiomics data were extracted from the gross tumor volumes (GTVs) identified on the planning CT, with gray level being discretized using three different bin widths (8, 16, and 32). The data extracted for the groups with and without distant metastasis were subsequently balanced using three different algorithms including synthetic minority over-sampling technique (SMOTE), adaptive synthetic sampling (ADASYN), and borderline SMOTE. From these different combinations, a total of nine radiomics datasets were derived. Top features that minimized redundancy while maximizing relevance to the endpoint were selected individually and collectively for the nine radiomics datasets to build support vector machine (SVM) based predictive classifiers. Performance of the developed classifiers was evaluated by receiver operating characteristic (ROC) curve analysis. (3) Results: of the 225 locally advanced HPV+ OPSCC patients being studied, 9.3% had developed distant metastases at last follow-up. SVM classifiers built for the nine radiomics dataset using either their own respective top features or the top consensus ones were all able to differentiate the two cohorts at a level of excellence or beyond, with ROC area under curve (AUC) ranging from 0.84 to 0.95 (median = 0.90). ROC comparisons further revealed that the majority of the built classifiers did not distinguish the two cohorts significantly better than each other. (4) Conclusions: radiomics demonstrated discriminative ability in distinguishing patients with locally advanced HPV+ OPSCC who went on to develop distant metastasis after completion of definitive chemoradiation or radiation alone and may serve to risk stratify this patient population with the purpose of guiding the appropriate therapy.

Mechanisms of metastasis and development of resistance to therapy in breast cancer. A clinical case of the effectiveness of ixabepilone in hormone-receptorpositive breast cancer with multidrug resistance

Metastatic breast cancer occupies a leading position in the structure of mortality among women with oncological diseases worldwide. At the same time, the control of metastatic disease remains a significant problem for clinical oncology despite the improvement of early screening indicators, as well as the introduction of targeted therapy in clinical practice. An increase in the tumor stemness and the epithelial-mesenchymal transition in the primary tumor leads to the plasticity of the tumor cell. This is realized in the progression of the disease, resistance to the therapy and the appearance of distant metastases. Numerous signaling pathways, including PI3K/APK, STAT3, Wnt, Hedgehog, and Notch, play a key role in maintaining cellular plasticity in breast cancer. Understanding the cellular mechanisms of breast cancer cell plasticity with the development of multidrug resistance is a prerequisite for the development of effective therapeutic strategies against metastatic breast cancer in late-line therapy. The article presents an overview of the current understanding of the biological mechanism of the metastatic cascade and resistance to therapy. It is from the point of view of the plasticity of the tumor cell and the increase in the stemness of the tumor that the resistance to treatment is considered. The effectiveness of the representative of Ixabepilone was analyzed in the case of its use in the late-line therapy of hormone-receptor-positive breast cancer with multidrug resistance.

A study of 24 cases of salivary gland carcinoma with distant metastasis.

Salivary gland carcinoma is a relatively rare disease of the head and neck. Although it frequently presents with distant metastases, few reports have been published on this subject. The present study investigated the prognosis of patients with distant metastases from salivary gland cancer. A total of 24 cases of salivary gland carcinoma with distant metastasis who were initially treated at the Department of Otolaryngology-Head and Neck Surgery of Nara Medical University during a 16-year period from August 2004 to July 2020 were included. The histopathological types included salivary duct carcinoma (8 cases), adenoid cystic carcinoma (6 cases), myoepithelial carcinoma (3 cases), Squamous cell carcinoma (2 cases), adenocarcinoma (2 cases), acinic cell carcinoma (2 cases) and mucoepidermoid carcinoma (1 case). A total of 18 patients had stage IV carcinoma, which represented the majority. Of all patients, ~80% developed distant metastases within 2 years of initial diagnosis. Survival rates after the appearance of distant metastases were 43.5% at 5 years and 14.5% at 10 years. The results of the current study revealed that no factors significantly influenced long-term prognosis after the development of distant metastases. In future, it may be necessary to re-examine these results in a larger sample size and standardise treatment methods as a result.

Clinical and histopathological risk factors for distant metastasis in head and neck cancer patients.

SUMMARYThe incidence of distant metastasis (DM) in head and neck squamous cell cancer (HNSCC) is relatively low. Multiple risk factors have been described for development of DM at baseline and after treatment. However, to date, there is no meta-analysis or systematic review investigating the relationships between clinical and histopathological factors and the appearance of DM in HNSCC patients. Among 1,272 eligible articles, 23 met inclusion criteria for qualitative analysis, and 6 for quantitative analysis. The meta-analysis on 5,353 patients showed that hypopharyngeal site, T3-T4 categories, extranodal extension, positive lymph node size > 6 cm, locoregional failure after previous treatment(s) and poor differentiation all significantly increase the risk of DM. According to our results, patients with the above-mentioned clinical and histopathological risk factors should be considered at high risk for DM and therefore submitted to strict pre-treatment assessment and undergo careful post-therapeutic follow-up.

Phyto-Immunotherapy, a Complementary Therapeutic Option to Decrease Metastasis and Attack Breast Cancer Stem Cells.

In this review, we report on the complexity of breast cancer stem cells as key cells in the emergence of a chemoresistant tumor phenotype, and as a result, the appearance of distant metastasis in breast cancer patients. The search for mechanisms that increase sensitivity to chemotherapy and also allow activation of the tumor-specific immune response is of high priority. As we observed throughout this review, natural products isolated or in standardized extracts, such as P2Et or others, could act synergistically, increasing tumor sensitivity to chemotherapy, recovering the tumor microenvironment, and participating in the induction of a specific immune response. This, in turn, would lead to the destruction of cancer stem cells and the decrease in metastasis.Source of Data: Relevant studies were found using the following keywords or medical subject headings (MeSH) in PubMed, and Google Scholar: “immune response” and “polyphenols” and “natural products” and “BCSC” and “therapy” and “metabolism” and “immunogenic cell death.” The focus was primarily on the most recent scientific publication.

Research progress on advanced renal cell carcinoma.

Renal cell carcinoma (RCC) is a malignant tumor and the third most common urinary disease. It was estimated that RCC affected over 350,000 individuals in 2013, and there are nearly 140,000 deaths annually due to this disease. The initial masses in RCC patients are mostly confined to a single organ. However, due to the metastatic spread of cancer cells through the circulatory system, more than 30% of RCC patients relapse after surgery. The appearance of distant metastases often means that patients enter the advanced stage of cancer with low quality of life and a short expected survival time. This review aims to describe the extant research on advanced RCC, including its pathophysiology, heterogeneity, diagnosis, treatment, and prospects. We try to highlight the most suitable means of treating advanced RCC patients, focusing on comprehensive personalized treatments.

Anaplastic thyroid cancer. Is there a light at the end of the tunnel?

Anaplastic thyroid cancer is one of the most prognostically unfavorable tumors. This disadvantage traditionally consisted of a rapid increase in the size of the primary tumor with a tendency to the development of asphyxia and the rapid appearance of distant metastases, as well as a poor response to the recommended treatment methods. The result of many years of efforts by oncologists around the world were several treatment regimens, including an ideal amount of surgical intervention, chemotherapy and radiation therapy, but the effectiveness of this treatment, as well as the patient’s life expectancy after it, could not be called satisfactory. Improving the understanding of the molecular genetic characteristics of tumors, including anaplastic thyroid cancer, provided us with information on two possible features of the genetic apparatus of tumor cells that can have clinical significance: V600E mutations in the BRAF gene and fusion of NTRK genes. The clinical example described in this article is probably the first Russian illustration of the effectiveness of anti-BRAF therapy in a patient with anaplastic thyroid cancer. From our point of view, the benefit of this example is not only to demonstrate the effectiveness of modern targeted therapy, but also the need not to abandon other treatment methods, in this case, radiation therapy to the area of the primary tumor (and by analogy with this, surgical removal of the thyroid tumor glands in case of its resectability).

Podoplanin promotes cancer-associated thrombosis and contributes to the unfavorable overall survival in an ectopic xenograft mouse model of oral cancer

BackgroundPodoplanin (PDPN) is a transmembrane glycoprotein that mediates tumor cell-induced platelets aggregation in different cancer types. Emerging data indicate that PDPN is a marker for poor prognosis of human oral squamous cell carcinoma (OSCC). However, the functional impacts of PDPN on cancer formation and disease progression of OSCC remain to be elucidated. MethodsThe sublines of the OECM-1 oral cancer cells with PDPN knockdown or overexpression were established. The cellular characteristics and the ability to induce platelet aggregation of these cells lines were analyzed. An ectopic xenograft animal model by inoculating cancer cells into the anterior neck region of nude mice was established to investigate the functional impact of PDPN on disease progression and cancer-associated thrombosis of OSCC. ResultsPDPN promoted OSCC cell migration and invasion, but had no effect on cell proliferation in vitro and tumor growth in vivo. Co-incubation of PDPN-positive (PDPN+) OSCC cells with platelets induced platelet activation and aggregation. The mice bearing PDPN+ tumor had a decrease in overall survival despite that there was no gross appearance of distant metastasis. A speckled immunofluorescence staining pattern of platelet marker mCD41 was defined in the PDPN+ tumor sections and the intensity was greater than in the PDPN-low or negative tumor sections. Co-immunofluorescence staining of the tumor sections with mCD41 and the endothelial cell marker mCD31 further demonstrated that platelet aggregates were located in the lumen of blood vessel and were also distributed intratumorally in the mice bearing PDPN+ tumors. ConclusionsThese data demonstrated that PDPN expression in the cancer cells is associated with high risk of thrombosis, leading to unfavorable overall survival of the mice. This study provides new insights into the functions of PDPN in cancer-associated thrombosis and in the pathophysiology of OSCC.

The effectiveness of chemotherapy in small cell lung cancer patients with BRCA2 gene mutation and Schwartz-Bartter syndrome

Small cell lung cancer (SCLC) currently comprises 15–20% of all lung cancers. It is characterised by rapid growth and early appearance of distant metastases. It is closely related to smoking. A characteristic feature of this type of cancer is the frequent coexistence of paraneoplastic syndromes (about 50% of patients). Paraneoplastic syndromes are clinically important because they can be the first sign of cancer. Early diagnosis of disturbing symptoms is an important factor in increasing the effectiveness of treatment and the patient’s chance for longer survival. The most frequent and important paraneoplastic syndromes in the course of SCLC are primarily the syndrome of inappropriate antidiuretic hormone hypersecretion (SIADH), paraneoplastic cerebellar degeneration, and Lambert-Eaton syndrome. This paper presents the case of a patient who came to the hospital with symptoms of hyponatraemia. Looking for the causes of hyponatraemia, the syndrome of abnormal secretion of antidiuretic hormone (Schwartz-Bartter syndrome) in the course of small cell lung cancer was confirmed. The fact that the patient was genetically burdened with the family history of breast cancer and was a carrier of the BRCA2 gene mutation was also significant. According to the latest research, mutation in the BRCA2 gene significantly affects the chemosensitivity of cancer cells, and thus increases the body’s response to treatment. The patient received chemotherapy with carboplatin and etoposide, resulting in partial remission of cancer after two treatment cycles.

Роль МРТ в выявлении экстрамуральной сосудистой инвазии как индикатора наличия регионарных и отдаленных метастазов рака нижнеампулярного отдела прямой кишки

Rectal cancer occupies one of the leading places in the structure of mortality in both sexes, with the only radical method of treatment is surgery. For the planning of surgical treatment, it is important to assess the metastatic lesion of the locoregional lymph nodes, the presence of extramural lymphovascular invasion, which is an important predictor of recurrence of the disease, as well as an indicator of the early appearance of distant metastases. The effectiveness and reliability of preoperative staging of the low rectal cancer has increased significantly after the introduction into clinical practice of magnetic resonance imaging, as well as a comprehensive preoperative radiation examination of patients. The article is devoted to the problems of preoperative staging and determination of statistically significant relationships between the presence of extramural vascular invasion in cancer of the low rectal cancer and the presence of distant metastases, the identification of the correlation between T and N - stages of the tumor, their morphological types with diagnosed extramural vascular invasion.

New Experimental Facts on the Influence of Secondary Immunodeficiency on the Morphology and Biological Activity of Colorectal Tumor.

Colorectal tumors were studied 5 months after carcinogen injection to outbred albino rats with secondary immunodeficiency by common histological and immunobiochemical methods with the use of monoclonal and polyclonal antibodies to Ki-67, Bcl-2, p53, and VEGF. Injection of carcinogen to intact animals led to the formation of adenocarcinomas with high and moderate cell differentiation in the colon, while injection of carcinogen to animals with immunodeficiency was associated with a 1.5-fold higher incidence of GRADE 2 and GRADE 3 adenocarcinomas with more aggressive morphological phenotype and appearance of distant metastases.

Predicting Outcomes From Radical Radiotherapy for Non-small Cell Lung Cancer: A Systematic Review of the Existing Literature.

Radical radiotherapy (RT) is a potentially curative treatment in non-small cell lung cancer (NSCLC) and is delivered in conventional 2-Gy fractions, hypofractionated and ablative stereotactic courses. No reliable, predictive biomarkers for the clinical events of local control, appearance of distant metastases and development of toxicity have been introduced in routine clinical practice. Such a test would enable the Radiotherapist to tailor the clinical management of individual patients, considering their pre-treatment characteristics, in order reduce the risk of recurrence or toxicity e.g., dose modification, accelerated fractionation, hypofractionation, or concurrent systemic therapy. The aim of this review was to map the published literature relating to investigations of the potential predictive value of patient or treatment characteristics in radical RT for NSCLC. These investigations should remain a research focus for disease control given the upward trends in lung cancer incidence, and for the avoidance of toxicity, given the survivorship afforded to the cohort of patients that do well with radical RT, or with the increasing range of systemic agents following metastatic relapse. The conclusion of the presented analysis is that there are no published, effective and validated predictive tools for estimation of risk of local/distant recurrence or toxicity after radical RT for NSCLC. The authors have identified an important space for future research in the field of lung cancer radiotherapy.

Osteosarcoma of the larynx: rare clinical case

We present a clinical case of osteosarcoma of the larynx. It is a rare and aggressive tumor characterized by frequent local recurrence and the appearance of distant metastases. This is the only one case of osteosarcoma of the larynx in N.N. Blokhin National Medical Research Center of Oncology for the period from 1988 to 2017.

The Results of the Combine Treatment of Patients with Liver Bilobar Metastases from Colorectal Cancer Using Radiofrequency Ablation.

Colorectal cancer (CRC) is the third most common cancer worldwide. The mortality from CRC remains very high. The main cause of such a high mortality is a disseminate process with the appearance of distant metastases. In this regard, the treatment of metastatic lesions is recognized as an important trend in modern oncology. The program of study included 176 patients with colorectal cancer after primary tumorremoval with the malignant progression-multiple (more than 4) bilobar liver metastases. The research was organized in Samara Regional Oncology Centre from 2001 to 2014. By the treatment method, patients were divided into two groups. Main group got the combined (chemotherapy + radiofrequency ablation (RFA)) treatment (n = 98). In control group, only chemotherapy was applied (n = 78). One-, two-, and three-year OS were 73.5, 25.1, and 7.2% in the main group and 39.6, 6.3, and 2.1% in the control group. The RFA application allowed us to reach the index of 4-year survival 1.8% in the main group, while we received only 2.1 of 3-year survival in the control group. The OS median reached 18months in the main group and 11months in the control group. So, the OS curves in two comparing groups were significantly different according to statistics (log-rank test 3.77, р = 0.000). The application of RFA in combination with chemotherapy in the treatment of bilobar metastasis colorectal cancer allows to improve the performance of disease-free survival and overall survival significantly, compared with the group of patients who received only chemotherapy.

Claudin-1 expression in cervical cancer.

Claudin-1 is a tight junction protein that has been demonstrated to be involved in tumorigenesis and tumor progression in various types of solid tumors. In the present study, the protein expression of claudin-1 in squamous cervical cancer tissues obtained from 106 patients was analyzed by immunohistochemistry. In addition, the grade of claudin-1 expression was analyzed for associations with certain clinicopathological parameters. A significant overexpression of claudin-1 was detected in the tumor cells, when compared with that in the peritumoral stroma. There was no significant association between claudin-1 expression and FIGO stage, tumor size, grading or the appearance of distant metastases. Cervical cancer patients scoring positive for claudin-1 protein expression tended to exhibit more lymph node metastasis (28.3%), compared with claudin-1-negative patients (7.1%). Regarding overall survival, the results of the present study suggest a better prognosis for claudin-1-negative patients. In order to elucidate whether claudin-1 overexpression has a significant prognostic impact on squamous cervical cancer, further studies are required.

COLORECTAL CANCER AND FEATURES OF ITS METASTASIS

The article analyzes the frequency of regional metastasis detection in patients with operative colorectal cancer as well as the frequency and patterns of the appearance of distant metastases depending on the presence or absence of regional metastases, tumor localization and the method of treatment. It was found that the frequency of distant metastases in colorectal cancer depended mainly on the presence or absence of metastases in the regional lymph nodes. Some influence on the decrease in the frequency of distant metastasis was exacerbated by the preoperative radiation exposure by radiomodifiers and on the increase - the interval between the end of the radiation treatment phase and the moment of surgery. In rectal cancer the localization of distant metastases depended on the level of tumor localization. In colon cancer the major part (81.6%) of distant metastases was located in the liver, the rest 18.4% -extrahepatic and was represented by peritoneum dissemination, metastases in the ovary and retroperitoneal lymph nodes. Among colon cancer patients after the combined treatment there were no cases of tumor dissemination through the abdominal cavity and the appearance of lymphogenous metastases.