Frequency Of Distant Metastases Research Articles

Real world outcomes of 2,339 patients with early-stage triple-negative breast cancer (TNBC) treated in British Columbia.

e23274 Background: TNBC represents 15-20% of all breast cancers, and tends to exhibit more aggressive features, more frequent distant metastasis and overall worse prognosis than other breast cancer subtypes. The treatment landscape for early-stage TNBC has changed considerably in the last decade, with new additions to neoadjuvant therapy (NAT) aimed at improving pathologic responses and outcomes. In this study, we assess real world data regarding treatment and outcomes in those with early-stage TNBC. Methods: The BC Cancer Breast Cancer Outcomes Unit database contains prospectively collected data on patients residing in British Columbia and diagnosed with breast cancer since 1989. This retrospective study evaluated patients diagnosed with stage I-III TNBC from 2010 to 2019. During this era, regimens containing anthracyclines and taxanes were routinely used. TNBC was defined as per ASCO-CAP guidelines as ER≤1%, PR≤1% and negative HER 2 (0, 1+ by immunohistochemistry, or 2+ ISH negative). Outcomes of interest included event free survival (EFS), overall survival (OS), and pathologic complete response (pCR). Results: 2,339 patients withstage I-III TNBC were identified with a mean follow up of 6.5 years. OS was 87% (95% CI 85-88%) at 3-years and 79% (95% CI 77-80%) at 5-years. The presenting stage was a significant prognostic factor, with 5-year EFS of 89%, 81% and 51%- and 5-year OS of 90%, 80%, and 53% for stages I, II, and III, respectively. There was an increase in NAT use in 2019 (n = 82/230,35.7%) when compared to 2010 (n = 20/227, 8.8%). The most common neoadjuvant regimens used included anthracycline and taxane chemotherapies (n = 343,81.4%), with only a small number receiving neoadjuvant platinum chemotherapy (n = 52, 12.4%). Pathological complete response (pCR) was achieved in 24.5% (103/421) of patients who received NAT. Patients with pCR had improved 5- year EFS (91% vs. 57%, HR 0.26 [95% CI 0.15-0.45]) and 5-year OS (90% vs. 59%, HR 0.26 [95% CI 0.15-0.45]) compared to those with residual disease. The subgroup that received salvage capecitabine had a poor 3-year EFS at 22% but was enriched for patients with residual nodal disease after NAT (n = 77/130, 59.2%). Conclusions: This real-world study of TNBC in the era prior to routine immunotherapy (IO), highlights the poor prognosis of TNBC, particularly patients with locally advanced disease and those who did not achieve pCR, despite adjuvant capecitabine. This stresses the need for advances in NAT and salvage therapies for TNBC with residual disease at high risk of recurrence. [Table: see text]

Abstract 880: Identifying ANKRD22 and fostamatinib as a theragnostic target and drug candidate for metastatic pancreatic cancer through in silico analysis

Abstract Introduction: Pancreatic cancer (PC) presents significant clinical challenges, marked by a low 5-year survival rate and frequent distant metastasis. When PC metastasizes to other organs, it leads to a notable decrease in the 5-year survival rate for PC in metastasis, dropping from 11% to 3%. Despite the effectiveness demonstrated by advanced anti-cancer therapies targeting these mutated genes, the improvement in survival rates remains modest. Another critical consideration is the rising resistance to Gemcitabine, a standard drug used for treating PC. Hence, it is imperative to gain a more profound understanding of the comprehensive mechanisms underlying metastatic pancreatic cancer (mPC) and actively explore novel drugs for its treatment. Methods: First, we reanalyzed the RNA-seq of three of PC's most common metastatic sites, including liver, lung, and peritoneum. Using the Galaxy platform, we identified DEGs (differentially expressed genes) between metastatic sites. After that, we further utilized other web-based tools and databases, such as GEPIA, TIMER 2.0, Alphafold, PubChem, Drugbank, and Chembl, to identify ANKRD22 and perform molecular docking of Fostamatinib binds to this gene. Results: Our research focused on exploring the role of ANKRD22, which contains four copies of L-shaped ankyrin motifs, an emerging oncogenic molecule associated with various cancers. In the current study, we identified that ANKRD22 exhibited significant expression in the pancreatic adenocarcinoma (PAAD) cohort, correlating with deteriorating OS rates in PC patients. Moreover, it displayed distinct expression patterns in advanced stages of the disease compared to early stages, Furthermore, we uncovered a noteworthy correlation between ANKRD22 and the Kras, TP53, CDKN2A, and SMAD4 genetic anomaly, linked to diminished survival rates, as widely recognized, in the initiation and progression of PC, these four genes stand out as the most frequently mutated. Mechanistically, ANKRD22 exhibited associations with KRAS dependency signature, U12 type spliceosome assembly, multivesicular body routing, cell invasion, tumor cell line invasion, and tumor cell line migration, all indicative of PC progression and dissemination. Expanding our investigation through the DrugBank and ChEMBL databases, we delved into fostamatinib, an FDA-approved drug known as a spleen tyrosine kinase (SYK) inhibitor. Molecular docking experiments revealed the potential interaction between ANKRD22 and fostamatinib, suggesting its candidacy to treat mPC. Conclusion: Our findings identify ANKRD22 as a pivotal oncogenic factor promoting metastasis in PC and propose fostamatinib as a potential inhibitory treatment. Citation Format: Huong Thi Luu Kim Huynh, Hendrick Gao-Min Lim, Yuan-Chii Gladys Lee, Chien-Hsin Chen, Alexander T.H. Wu. Identifying ANKRD22 and fostamatinib as a theragnostic target and drug candidate for metastatic pancreatic cancer through in silico analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 880.

Abstract B036: Exploration of the human leukocyte antigen immunopeptidome in pancreatic adenocarcinoma

Abstract Pancreatic adenocarcinoma (PDAC) is a lethal disease with an 11% five-year survival rate and frequent distant metastasis at diagnosis. The immune escape mechanisms driving this unchecked proliferation in PDAC remain unclear. The HLA system plays a crucial role in immune-mediated recognition of neoplasms. HLA class I presents endogenously processed peptides to circulating CD8+ T-cells, while HLA class II presents exogenous peptides to CD4+ T-cells, with the collective sum of these peptides known as the immunopeptidome. Most immunopeptidome studies rely on peptides derived solely from cell lines, with few peptides directly reported from patients. Characterization of the immunopeptidome in cancer patients is critical for understanding peptide presentation and neoantigen recognition in PDAC. We hypothesize that isolating HLA class I and II peptides directly from PDAC donors will identify novel neoantigen-derived peptides presented to the immune system with high fidelity for specific HLA alleles. Whole Exome Sequencing (WES) was performed on nine PDAC donors from the UNMC Rapid Autopsy Program. Somatic mutations were identified using best practices published by the BROAD Institute. HLA alleles were identified with the HLA-HD algorithm. Large-scale immunopurification of HLA class I complexes and associated peptides was performed on PDAC liver metastases. Data-Dependent-Acquisition MS/MS with PEAKS analysis identified individual peptide sequences. Similar strategies are being employed for HLA class II peptide isolation from matched donor spleens. To date 39,639 HLA class I peptides and 2,995 HLA class II peptides have been identified from nine donors. Of HLA class I isolated peptides, 9,987 unique sequences have been traced and mapped to the human reference genome. Of the remaining 29,652 unmapped peptides, we have manual confirmation of the presence of neoantigen-derived peptides within that pool, with a pipeline for large scale alignment of these peptides to the annotated mutated genome pending. The gold standard HLA-peptide predictive binding algorithm, netMHC, confirms that 24.2% of our isolated HLA class I peptides are predicted binders for their patient-specific HLA alleles. A notable finding is that 9% of identified HLA class II peptide sequences contained sequences identical to those isolated during independent HLA class I isolations from the same donor. These data establish the high-fidelity of our pipeline for identification of peptides presented by the HLA system directly from PDAC donors. The quantity of HLA-associated peptides discovered sets this study on track to surpass all previously reported patient-derived immunopeptidome studies. The observed conservation of HLA class I and II sequences from independent isolations within the same donor implicates a novel mechanism by which specific combinations of HLA class I and II alleles shape the immunopeptidome. Further work identifying neoantigens in our unmatched isolated HLA class I and II peptides will be continued to uncover potential novel targets for future immunotherapies. Citation Format: William R. Miklavcic, Paul Grandgenett, Michael A. Hollingsworth. Exploration of the human leukocyte antigen immunopeptidome in pancreatic adenocarcinoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr B036.

The law of paired cases on the example of adenocystic cancer of salivary glands tissue with multicentric growth of different locations

Adenoid cystic cancer of the salivary glands is characterized by recurrent and/or metastatic course. Compared with other histological types of salivary gland cancer, it usually has a more latent clinical course with a low incidence of spread to regional lymph nodes. However, after removal of the primary tumor, local and distant relapses are quite common. In addition, the presence of prognostic factors such as metastases in the lymph nodes of the neck, low degree of tumor differentiation, perineural and lymphovascular invasion contributes to an increase in the frequency of distant metastasis with a poor prognosis.
 Cases of atypical arrangement of salivary gland tissues with extranodal heterotopia are rare. In the head and neck region, different localizations of heterotopia of salivary gland tissues have been described, but the pterygopalatine fossa was not mentioned in the available sources. The difficulty of histological diagnosis when verifying heterotopia of the salivary glands may be due to the phenomena of chronic inflammation, lymphoid infiltration, tissue fibromatosis and the development of metaplasia. The rare occurrence of heterotopia of the salivary glands, the difficulties of its diagnosis and the lack of a unified approach to surgical treatment require consideration of each individually identified case.
 The law of paired cases (also known as the law of series) is implemented in the interpretation of the presented clinical cases, when the identification of individual extraorgan foci of adenoid cystic cancer of the pterygopalatine space may be associated with a rare extranodal heterotopia of salivary gland tissue. The primary multiplicity of malignant lesions of the major salivary glands and heterotopia of salivary gland tissue can be both synchronous and metachronous. Adenoid cystic cancer of the pterygomaxillary fossa, as a component of multicentric growth of various localizations, clinically confirmed the recurrent nature of the course, the tendency to distant metastasis and generalization of the malignant process.

Benefit of postoperative regional nodal irradiation in patients receiving preoperative systemic therapy with docetaxel/carboplatin/trastuzumab/pertuzumab for HER2-positive breast cancer

AimThe role of regional nodal irradiation (RNI) after preoperative systemic treatment (PST) with targeted therapy for HER2-positive breast cancer remains uncertain. This study aimed to investigate the impact of RNI on locoregional recurrence (LRR) and disease-free survival (DFS) outcomes after docetaxel/carboplatin/trastuzumab/pertuzumab (TCHP) for PST. MethodsWe retrospectively analyzed 255 patients who were treated with six cycles of TCHP between 2016 and 2019. The patients were divided into four groups based on clinical nodal involvement: group A, with no nodal disease; group B, with axillary lymph node (AXL) level I; group C, with AXL level I with II/III; and group D, with supraclavicular or internal mammary nodes. ResultsThe RNI group had more advanced nodal disease (C/D) than the no RNI group (56.9 % vs. 6.8 %). With a median follow-up of 51.3 months, there were two (0.8 %), three (1.2 %), and 15 (5.9 %) local, regional, and distant metastases, respectively. LRR did not differ significantly according to the RNI (2.6 % vs. 1.0 %, p = 0.651). Group D had the most frequent distant metastases (17.5 %; p = 0.005). The 4-year DFS rate was 92.7 %, and DFS did not improve significantly after RNI (p = 0.074). When stratified by clinical nodal groups and pathological axillary response, RNI had no effect on LRR/DFS outcomes. ConclusionWith a rare incidence of LRR, RNI did not significantly affect LRR or DFS in patients with HER2-positive breast cancer after with PST-TCHP. However, intensive systemic treatment is required for advanced diseases (C/D). Selective de-intensified RNI and intensified systemic treatment should be investigated in future studies.

Determination of Risk Factors for Postoperative Acute Kidney Injury in Patients With Gynecologic Malignancies.

Background Postoperative acute kidney injury (AKI) is an important cause of mortality and morbidity among surgical patients. There is little information on the occurrence of AKI after operations for gynecologic malignancies. This study aimed to determine the incidence of AKI in patients who underwent surgery for gynecological malignancies and determine the risk factors in those who developed postoperative AKI. Methodology A total of 1,000 patients were enrolled retrospectively from January 2007 to March 2013. AKI was defined according to the Kidney Disease Improving Global Outcomes 2012 Clinical Practice Guideline for Acute Kidney Injury. Perioperative variables of patients were collected from medical charts. Results The incidence of postoperative AKI was 8.8%, with stage 1 occurring in 5.9%, stage 2 in 2.4%, and stage 3 in 0.5% of the patients. Patients who had AKI were significantly older, had higher body mass index (BMI) higher preoperative C-reactive protein (CRP) levels, and more frequently had a history of distant organ metastasis when compared with those who did not have AKI. When compared with patients who did not develop AKI postoperatively, longer operation times and intraoperative usage of higher amounts of erythrocyte suspension and fresh frozen plasma were seen in those who developed AKI. Conclusions Patients who had AKI were older, had higher BMI with higher preoperative CRP levels, more frequent distant organ metastasis, longer operation times, and higher amounts of blood transfused intraoperatively. Defining preoperative, intraoperative, and postoperative risk factors for postoperative AKI and taking necessary precautions are important for the early detection and intervention of AKI.

Castration-resistant prostate cancer (CRPC) on PSMA-PET: Imaging features, disease distribution, and a comparison to castration-sensitive prostate cancer (CSPC).

e17062 Background: 18F-DCFPyL PET/CT is increasingly used in the staging and response assessment of patients (pts) with prostate cancer. Recent studies suggest that short-term ADT increases prostate-specific membrane antigen (PSMA) expression, whereas long-term ADT suppresses PSMA. Changes in PSMA expression after the development of CRPC are uncertain. We described 18F-DCFPyL PET findings in pts with CRPC and compared them to findings in CSPC. Methods: We analyzed 538 18F-DCFPyL scans performed at our large academic center. CRPC was defined as rising PSA w/ testosterone < 50 ng/dL on ADT. M0 CRPC was defined as absence of extra-pelvic disease (dz) and oligometastatic CRPC (oCRPC) was defined as ≤ 5 LN + osseous lesions and absence of visceral dz. Highest SUV max (hSUVmax) was abstracted from radiologist impression. Means between groups were compared using two-tailed t-tests; undetectable PSA levels were scored as “0”. Logistic regression was used to compare dz distribution between castrate states. Significance was defined as p < 0.05. Results: There were 81 pts with CRPC, 72 pts with metastatic CRPC (mCRPC) and 123 pts with mCSPC. The median ages of pts with mCRPC (74.5 years) and mCSPC (71) were similar. The mean PSAs of mCSPC (20.2 ng/mL) and mCRPC (69.4) were significantly different. hSUVmax was higher in mCRPC (mean 40.3, 95% CI 32.7 – 47.8) than in mHSPC (22.6, 18.4 – 26.9), p < 0.001. Distribution of mCRPC lesions was as follows: prostate bed (26.4%), local pelvic LN (25%), distant LN (M1a, 41.7%), osseous (M1b, 16.7%), and visceral (M1c, 16.7%). In a multivariate analysis mCRPC pts had lower rates of pelvic LN dz and higher rates of M1c, with a trend toward increased M1b (p < 0.10), compared to mCSPC pts. ADT and androgen pathway inhibition did not affect hSUVmax in CRPC. Within CRPC, there were 9 pts with M0 dz, 24 pts with oCRPC, and 48 pts with polymetastatic dz (pmCRPC). The ages (Table) of pmCRPC and oCRPC pts were similar. The mean PSA of pmCRPC (100.9) was higher than that of oCRPC (8.8) and M0 CRPC (5.7). hSUVmax between oCRPC (40.3) and pmCRPC (40.3) was similar. Conclusions: The greater hSUVmax in mCRPC may implicate the effect of ADT on PSMA expression or may describe differing tumor biology. mCRPC pts had less local dz and more frequent distant metastases, likely reflecting more advanced disease. These findings will help inform detection of developing castrate resistance on PSMA-PET. More data are needed on the classification of oligometastatic dz on PSMA-PET and the impact of hormone therapy on PSMA in CRPC. [Table: see text]

Predictive Value of Total Metabolic Tumor Burden Prior to Treatment in NSCLC Patients Treated with Immune Checkpoint Inhibition.

We aimed to assess the predictive value of the total metabolic tumor burden prior to treatment in patients with advanced non-small-cell lung cancer (NSCLC) receiving immune checkpoint inhibitors (ICIs). Pre-treatment 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography/computed tomography (PET/CT) scans performed in two consecutive years for staging in adult patients with confirmed NSCLC were considered. Volume, maximum/mean standardized uptake value (SUVmax/SUVmean), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were assessed per delineated malignant lesion (including primary tumor, regional lymph nodes and distant metastases) in addition to the morphology of the primary tumor and clinical data. Total metabolic tumor burden was captured by totalMTV and totalTLG. Overall survival (OS), progression-free survival (PFS) and clinical benefit (CB) were used as endpoints for response to treatment. A total of 125 NSCLC patients were included. Osseous metastases were the most frequent distant metastases (n = 17), followed by thoracal distant metastases (pulmonal = 14 and pleural = 13). Total metabolic tumor burden prior to treatment was significantly higher in patients treated with ICIs (mean totalMTV ± standard deviation (SD) 72.2 ± 78.7; mean totalTLG ± SD 462.2 ± 538.9) compared to those without ICI treatment (mean totalMTV ± SD 58.1 ± 233.8; mean totalTLG ± SD 290.0 ± 784.2). Among the patients who received ICIs, a solid morphology of the primary tumor on imaging prior to treatment was the strongest outcome predictor for OS (Hazard ratio HR 28.04, p < 0.01), PFS (HR 30.89, p < 0.01) and CB (parameter estimation PE 3.46, p < 0.01), followed by the metabolic features of the primary tumor. Interestingly, total metabolic tumor burden prior to immunotherapy showed a negligible impact on OS (p = 0.04) and PFS (p = 0.01) after treatment given the hazard ratios of 1.00, but also on CB (p = 0.01) given the PE < 0.01. Overall, biomarkers on pre-treatment PET/CT scans showed greater predictive power in patients receiving ICIs, compared to patients without ICI treatment. Morphological and metabolic properties of the primary tumors prior to treatment in advanced NSCLC patients treated with ICI showed great outcome prediction performances, as opposed to the pre-treatment total metabolic tumor burdens, captured by totalMTV and totalTLG, both with negligible impact on OS, PFS and CB. However, the outcome prediction performance of the total metabolic tumor burden might be influenced by the value itself (e.g., poorer prediction performance at very high or very low values of total metabolic tumor burden). Further studies including subgroup analysis with regards to different values of total metabolic tumor burden and their respective outcome prediction performances might be needed.

Hemicolectomy versus appendectomy for patients with appendiceal neuroendocrine tumours 1-2 cm in size: a retrospective, Europe-wide, pooled cohort study.

Awareness of the potential global overtreatment of patients with appendiceal neuroendocrine tumours (NETs) of 1-2 cm in size by performing oncological resections is increasing, but the rarity of this tumour has impeded clear recommendations to date. We aimed to assess the malignant potential of appendiceal NETs of 1-2 cm in size in patients with or without right-sided hemicolectomy. In this retrospective cohort study, we pooled data from 40 hospitals in 15 European countries for patients of any age and Eastern Cooperative Oncology Group performance status with a histopathologically confirmed appendiceal NET of 1-2 cm in size who had a complete resection of the primary tumour between Jan 1, 2000, and Dec 31, 2010. Patients either had an appendectomy only or an appendectomy with oncological right-sided hemicolectomy or ileocecal resection. Predefined primary outcomes were the frequency of distant metastases and tumour-related mortality. Secondary outcomes included the frequency of regional lymph node metastases, the association between regional lymph node metastases and histopathological risk factors, and overall survival with or without right-sided hemicolectomy. Cox proportional hazards regression was used to estimate the relative all-cause mortality hazard associated with right-sided hemicolectomy compared with appendectomy alone. This study is registered with ClinicalTrials.gov, NCT03852693. 282 patients with suspected appendiceal tumours were identified, of whom 278 with an appendiceal NET of 1-2 cm in size were included. 163 (59%) had an appendectomy and 115 (41%) had a right-sided hemicolectomy, 110 (40%) were men, 168 (60%) were women, and mean age at initial surgery was 36·0 years (SD 18·2). Median follow-up was 13·0 years (IQR 11·0-15·6). After centralised histopathological review, appendiceal NETs were classified as a possible or probable primary tumour in two (1%) of 278 patients with distant peritoneal metastases and in two (1%) 278 patients with distant metastases in the liver. All metastases were diagnosed synchronously with no tumour-related deaths during follow-up. Regional lymph node metastases were found in 22 (20%) of 112 patients with right-sided hemicolectomy with available data. On the basis of histopathological risk factors, we estimated that 12·8% (95% CI 6·5 -21·1) of patients undergoing appendectomy probably had residual regional lymph node metastases. Overall survival was similar between patients with appendectomy and right-sided hemicolectomy (adjusted hazard ratio 0·88 [95% CI 0·36-2·17]; p=0·71). This study provides evidence that right-sided hemicolectomy is not indicated after complete resection of an appendiceal NET of 1-2 cm in size by appendectomy, that regional lymph node metastases of appendiceal NETs are clinically irrelevant, and that an additional postoperative exclusion of metastases and histopathological evaluation of risk factors is not supported by the presented results. These findings should inform consensus best practice guidelines for this patient cohort. Swiss Cancer Research foundation.

High-Grade Sarcomas with Myogenic Differentiation Harboring Hotspot PDGFRB Mutations

PDGFRB-activating mutations have been reported in pediatric myofibroma and myofibromatosis. However, recurrent gain-of-function PDGFRB mutations have not been documented in sarcomas with myogenic differentiation. Driven by occasional sarcomas harboring PDGFRB mutations, we investigated their prevalence and clinicopathologic and genomic features in a large cohort of sarcomas. An institutional targeted DNA next-generation sequencing database was searched for sarcomas with myogenic differentiation harboring hotspot PDGFRB gene alterations. Among 3300 patients with sarcomas, 21 (0.6%) patients were identified (17 women, 4 men) with an age range of 35 to 88 years. The site distribution included 13 gynecologic tract (12 uteri, 1 vagina), 4 bone and soft tissue, and 4 viscera. All except 1 were high grade. Most patients were diagnosed as sarcomas with myogenic differentiation based on partial staining for 1 or more muscle markers, whereas 6 were labeled as leiomyosarcoma (LMS). Most tumors showed monomorphic spindle morphology, with either heterogeneous features of myofibroblastic and smooth muscle differentiation or an undifferentiated phenotype. Hormone receptors were negative in all uterine cases. PDGFRB immunostaining in all cases tested was strong and diffuse, whereas PDGFRA was negative/focal. The most frequent PDGFRB mutations were exon 12 (43%), exon 14 (N666K/S/T) (38%), and exon 18 (D850Y/H/V or insertion/deletion) (19%). The most frequent co-existing genetic alterations (26% to 37%) occurred in CDKN2A/B, TP53, TERT, and MED12. Moreover, PDGFRB-mutant sarcomas had an overall distinct genomic landscape compared with both uterine and soft tissue LMS control groups. These tumors were associated with a highly aggressive clinical course, with frequent distant metastases (81%) and death (76%), regardless of anatomic location, and worse overall survival compared with the 2 LMS control groups. This is the first study documenting recurrent hotspot PDGFRB alterations in high-grade sarcomas, which show a predilection for uterine location and myogenic differentiation that fall short of the diagnostic criteria for LMS. Further studies are needed to investigate the therapeutic potential of kinase inhibitors in this group of tumors.

BREAST CANCER IN OBESITY: MENOPAUSAL STATUS AND REDOX CHARACTERISTICS OF ADIPOSE TISSUE DYSFUNCTION

Summary. Aim: to investigate the levels of superoxide radical (SR) generation and matrix metalloproteinase activity in tumor and adipose tissue adjacent to the tumour (ATA) depending on BMI and menopausal status of breast cancer patients. Object and methods: tumor tissue samples and ATA (postoperative material) from 70 women with breast cancer were studied. The methods used were EPR spectrometry, polyacrylamide gel zymography, general clinical and statistical methods. Results: a significant difference (p &lt; 0.05) in the rate of SR generation at normal weight and obesity was observed in postmenopausal patients, both in the tumour (1.6 times) and in the АТА (1.7 times); there is a significant difference (p &lt; 0.05) in the total activity of MMP-2 and -9 at normal weight and obesity, both in the tumour (2.2 times) and in the АТА (1.9 times). In premenopausal patients with breast cancer with overweight and normal weight do not differ significantly in the frequency of distant metastasis and the overall survival. Рostmenopausal patients with obesity were characterized by a significant (p &lt; 0.05) increase in the frequency of distant metastasis and a decrease in the overall survival. At levels of MMP-2 activity in the ATA above 2.8 units, patients had a significantly shorter life expectancy (p = 0.02) and a higher risk of adverse disease outcome (HR = 2.9) than at lower levels of enzyme activity. Conclusion: the results obtained indicate the prospects for further research and the possibility of using these factors of the tumour microenvironment (SR generation and MMP activity in tumor tissue and ATA) as effective markers of breast cancer prognosis in the presence of overweight.

Guidelines for Evaluating Treatment Response Based on Bone Scan for Metastatic Castration-Resistant Prostate Cancer: Prostate Cancer Clinical Trial Working Group 3 Recommendations

In prostate cancer, the bone is the most common site of metastasis, and it is essential to evaluate metastatic bone lesions to assess the tumor burden and treatment response. Castration-resistant prostate cancer refers to the state wherein the cancer continues to progress despite a significant reduction of the sex hormone level and is associated with frequent distant metastasis. The Prostate Cancer Working Group 3 (PCWG3) released guidelines that aimed to standardize the assessment of treatment effects in castration-resistant prostate cancer using bone scintigraphy. However, these guidelines can be challenging to comprehend and implement in practical settings. The purpose of this review was to provide an overview of a specific image acquisition method and treatment response assessment for bone scintigraphy-based evaluation of bone lesions in metastatic castration-resistant prostate cancer, in accordance with the PCWG3 guidelines.

Efficacy of preoperative therapy in patients with high and low risk of distant metastasis in non-small cell lung cancer

Background. To select the optimal treatment for non-small cell lung cancer (NSCLC), it is important to predict the risk of distant metastasis and the effectiveness of therapy. The effect of neoadjuvant chemotherapy (NAC) on distant metastasis remains poorly understood. In this study we evaluated the feasibility of predicting the risk of distant metastasis and effectiveness of various treatment options for pre- and intraoperative therapy in NSCLC patients with high and low risk of distant metastasis, divided based on the assessment of morphological changes in the epithelium of small bronchi located near the primary tumor.Material and Methods. The study included 171 patients with NSCLC (T1-4N0-3M0). Various premalignant lesions: isolated basal cell hyperplasia (BCH+SM-D-), basal cell hyperplasia with squamous cell metaplasia (BCH+SM+D-) and squamous cell metaplasia with dysplasia (BCH-SM+D+) were identified in the bronchial epithelium of small bronchi taken at a distance of 3–5 cm from the tumor. Preliminary studies have shown that the detection of BCH+SM-D- or BCH-SM+D-in small bronchi are the markers of high risk of NSCLC distant metastasis, and the detection of BCH+SM+D- and BCH-SM-D- are the markers of low risk of NSCLC distant metastasis. 52.6 % of patients (90/171) received 2–3 courses of neoadjuvant chemotherapy (NAC), 41.1 % (37/90) of patients underwent intraoperative radiation therapy (IORT) at a single dose of 10–15 Gy and 47.4 % (81/171) of patients received platinum-based adjuvant chemotherapy (AC).Results. Both treatment options (NAC+IORT+ and NAC+IORT–) effectively reduced the incidence of distant metastases in the high-risk group patients during the first 2 years of follow-up compared with the high-risk group patients who did not received therapy. In the low-risk group patients, distant metastases rarely occurred, regardless of the treatment option. Adjuvant chemotherapy was found to have no influence on the frequency of distant metastases. Metastasis-free and overall survival rates were better in the low-risk group patients or in patients who received the NAC+IORT+ regimen.Conclusion. Combination of NAC and IORT resulted in the increase in metastasis-free and overall survival rates.

Prognostic factors for overall survival and intracranial progression in patients with renal cancer metastasis into the brain after neurosurgical treatment

Introduction. Treatment of patients with brain metastases is an important problem that should be considered in the framework of combination approach. Introduction of new techniques of drug therapy as well as radiotherapy and neurosurgical treatment allows to significantly increase patient survival. Effective drug therapy and local control of brain metastases are of utmost importance in prediction of overall survival and patient quality of life.Aim. To investigate the prognostic factors for overall survival and intracranial progression (local recurrences, distant metastases) in patients with brain metastases of renal cancer after neurosurgical resection.Materials and methods. Retrospective analysis of the treatment results of 114 patients with metastatic brain lesions due to renal cancer who underwent neurosurgical resection (NSR) at the N. N. Blokhin National medical Research Center of Oncology was performed. Clinical data of 102 (89.5 %) of 114 patients for whom data on survival was available were evaluated. Among them, 80 (78.4 %) of patients died, 22 (21.5 %) are under observation. Extracranial disease status at the time of NSR was known in 82 (71.9 %) patients: 45 (54.8 %) patients had extracranial metastases, and 37 (45.1 %) did not. Total resection of brain metastases with perifocal and perivascular zones was performed in 92 (90.1 %) patients; in other cases, fragmental lesion resection was performed.Results. median overall survival after NSR was 13.8 months (95 % confidence interval 10.3–18.6). per study data, factors affecting overall survival of patients with brain metastases of renal cancer after neurosurgical resection were presence / absence of extracranial metastases and patient’s functional status. Local recurrences in the postoperative cavity after NSR were observed in 24 (21 %) of 114 patients. median time of local recurrence was not achieved. Statistically significant factor of high risk of recurrence in the postoperative cavity was presence of lesions with maximal diameter ≥2 cm. Development of new (distant) metastases was observed in 31 (27.2 %) of 114 patients. median survival without distant metastases in patients with brain metastases after NSR was not achieved. frequencies of distant metastases at 6, 12 and 24 months were 15.5; 24.1 and 35.8 % respectively. per multifactor analysis, factors affecting development of distant metastases in the brain after NSR are multiple metastatic brain lesions and presence of extracranial metastases.Conclusion. Neurosurgical resection in patients with cerebral metastases of renal cancer in the total group leads to median overall survival of 13.8 months. predictors of better overall survival are absence of extracranial metastases and high functional status.

Identification of hub genes for early detection of bone metastasis in breast cancer.

BackgroundGlobally, among all women, the most frequently detected and diagnosed and the most lethal type of cancer is breast cancer (BC). In particular, bone is one of the most frequent distant metastases 24in breast cancer patients and bone metastasis arises in approximately 80% of advanced patients. Thus, we need to identify and validate early detection markers that can differentiate metastasis from non-metastasis breast cancers.MethodsGSE55715, GSE103357, and GSE146661 gene expression profiling data were downloaded from the GEO database. There was 14 breast cancer with bone metastasis samples and 8 breast cancer tissue samples. GEO2R was used to screen for differentially expressed genes (DEGs). The volcano plots, Venn diagrams, and annular heatmap were generated by using the ggplot2 package. By using the cluster Profiler R package, KEGG and GO enrichment analyses of DEGs were conducted. Through PPI network construction using the STRING database, key hub genes were identified by cytoHubba. Finally, K-M survival and ROC curves were generated to validate hub gene expression.ResultsBy GO enrichment analysis, 143 DEGs were enriched in the following GO terms: extracellular structure organization, extracellular matrix organization, leukocyte migration class II protein complex, collagen tridermic protein complex, extracellular matrix structural constituent, growth factor binding, and platelet-derived growth factor binding. In the KEGG pathway enrichment analysis, DEGs were enriched in Staphylococcus aureus infection, Complement and coagulation cascades, and Asthma. By PPI network analysis, we selected the top 10 genes, including SLCO2B1, STAB1, SERPING1, HLA-DOA, AIF1, GIMAP4, C1orf162, HLA-DMB, ADAP2, and HAVCR2. By using TCGA and THPA databases, we validated 2 genes, SERPING1 and GIMAP4, that were related to the early detection of bone metastasis in BC.Conclusions2 abnormally expressed hub genes could play a pivotal role in the breast cancer with bone metastasis by affecting bone homeostasis imbalance in the bone microenvironment.

Role of locoregional disease in the definition of radioiodine refractory thyroid cancer

Definition of RAI refractory cancer does not include the cervical lymph nodes (LN) radioiodine (RAI) uptake status. The aim of this study is to assess the outcome and the frequency of distant metastases (DM) and RAI uptake status in patients with non-RAI-avid metastatic LN compared with patients having RAI-avid metastatic LN. A retrospective study of consecutive patients followed in Gustave Roussy institute between 1990 and 2015 who underwent at least one RAI therapy and one cervical LN relapse surgery with Proven pathology. Finding Study cohort consisted of 145 patients [58.6 % females, median age at diagnosis of 38 years, papillary 135 (93 %), median follow-up of 14 years (2–42)]. All patients underwent total thyroidectomy and at least one RAI administration. Seventy-seven (53 %) patients disclosed uptake in neck LN (LN-RAI-pos) and 68 did not have any RAI uptake or disclosed a heterogeneous uptake (overall considered LN-RAI-neg). The risk of structural incomplete response at the last assessment was greater in LN-RAI-neg patients (38 %) compared with LN-RAI-pos patients (13 %) (p 0.0005). LN-RAI-neg was associated with an increased risk of DM compared with patients with LN-RAI-pos (35 % vs 18 % OR 2.4 95 %CI : 1.0747–5.715 ; p 0.024). The risk of occurrence of DM not disclosing RAI uptake was higher in the LN-RAI-neg group compared with the LN-RAI-pos group (58 % vs. 21 %, OR 89.4 95 %CI 6.1202–6154.8943 ; p < 0.0002). LN-RAI-neg status is significantly associated to a worse patient outcome and to the occurrence of DM and RAI-refractory DM.

Nasopharyngeal Cancer in Childhood, Case report

Nasopharyngeal carcinoma (NPC) is the most frequent cancer that begins in the nasopharynx and spreads to the head and neck in adults. In individuals with nasopharyngeal cancer, the outcome after medical intervention can be relatively excellent if they receive adequate and effective treatment. NPC, on the other hand, is extremely rare in childhood, and its prevalence rises with patient age. In general, NPC has a more aggressive character, with frequent distant metastases during the early stages of the disease in childhood. Keywords: Nasopharyngeal Carcinoma; Childhood; Head and Neck Cancer Abbreviations: NPC: Nasopharyngeal Carcinoma, CT: Computerized Tomography, EBV: Epstein-Barr Virus, PCR: Polymerase Chain Reaction, WHO: World Health Organization, SEER: Surveillance, Epidemiology and End Outcomes, OS: Overall Survival

Possible Metastatic Stage-Dependent ILC2 Activation Induces Differential Functions of MDSCs through IL-13/IL-13Rα1 Signaling during the Progression of Breast Cancer Lung Metastasis.

Simple SummaryWhen breast cancer metastasizes to the lung, group 2 innate lymphoid cells (ILC2s) are thought to promote tumor growth via the activation of myeloid-derived suppressor cells (MDSCs). In this study, we aimed to characterize the dynamic interactions of ILC2s and MDSCs during the course of cancer progression from the micrometastatic to the macrometastatic stages. We found that ILC2s were activated in both the micro- and macrometastatic regions, suggesting sustained activation throughout the metastatic cascades. In addition, our findings indicate that ILC2s may induce the immunosuppressive functions of MDSCs during the later stages of metastasis. Concomitantly, ILC2 may instigate extracellular matrix remodeling by polymorphonuclear (PMN)-MDSC activation during the early stages of metastasis. These metastatic-stage-specific changes may contribute to metastatic tumor growth in the microenvironment of breast cancer lung metastasis.Breast cancer is the most common cancer in women worldwide, and lung metastasis is one of the most frequent distant metastases. When breast cancer metastasizes to the lung, group 2 innate lymphoid cells (ILC2s) are thought to promote tumor growth via the activation of myeloid-derived suppressor cells (MDSCs), which are known to negatively regulate anticancer immune responses. However, it remains to be elucidated exactly how this ILC2–MDSC interaction is involved in tumor growth during metastases formation. Using a 4T1/LM4 breast cancer mouse model, we found that ILC2s were activated in both the micro- and macrometastatic regions, suggesting sustained activation throughout the metastatic cascades via IL-33/ST2 signaling. Consistent with IL-13 secretion from activated ILC2s, the frequencies of polymorphonuclear (PMN)- and monocytic (M)-MDSCs were also significantly elevated during the progression from micro- to macrometastatic cancer. However, the effects of ILC2-induced MDSC functionality on the microenvironment differed in a metastatic-stage-specific manner. Our findings indicate that ILC2s may induce the immunosuppressive functions of MDSCs during the later stages of metastasis. Concomitantly, ILC2 may instigate extracellular matrix remodeling by PMN-MDSC activation during the early stages of metastasis. These metastatic-stage-specific changes may contribute to metastatic tumor growth in the microenvironment of breast cancer lung metastasis.

Clinical Features of Recurrence Pattern with Lung Metastasis After Radical Esophagectomy for Thoracic Esophageal Cancer.

One of the difficulties in the treatment of esophageal cancer surgery is the high rate of postoperative recurrence. After esophagectomy, distant metastatic recurrence frequently occurs in the lung. This study aimed to determine the clinical features of a recurrence pattern with lung metastasis. The current study analyzed data from 138 patients who had postoperative recurrence of esophageal cancer after a radical esophagectomy. According to the recurrence pattern at the time of initial diagnosis, the patients were classified into two groups as follows: those with lung metastasis and those without. Twenty-three of the 138 investigated patients had a recurrence pattern with lung metastasis. Salvage surgery and postoperative pneumonia (p = 0.041 and 0.030, respectively) were identified as risk factors for recurrence pattern with lung metastasis in multivariate analysis. When we compared the sites of primary esophageal tumors, we found that the frequencies of distant metastases, such as lung and liver metastases, as well as pleural/peritoneal dissemination, were higher in the mid and distal esophageal tumors. Patients with a recurrence pattern showing lung metastasis alone had a better overall and post-recurrence survival than those with other recurrence patterns (p < 0.001 and p < 0.001). In patients who had postoperative recurrence after esophagectomy for thoracic esophageal cancer, salvage surgery, and postoperative pneumonia were significantly related to recurrence pattern with lung metastasis. Postoperative recurrence with lung metastasis alone had a better prognosis than other recurrence patterns; therefore, when pulmonary recurrence is suspected, performing intensive examinations for early diagnosis is critical.

Homogeneous and heterogeneous risk and prognostic factors for lung metastasis in colorectal cancer patients

BackgroundThe lung is one of the most frequent distant metastasis sites in colorectal cancer (CRC) patients; however, lung metastasis risk and prognostic factors have not been comprehensively elucidated. This study aimed to identify the homogeneous and heterogeneous lung metastasis risk and prognostic factors in CRC patients using the Surveillance, Epidemiology, and End Results (SEER) database.MethodsCRC patients registered in the SEER database between 2010 and 2016 were included to analyse risk factors for developing lung metastasis by using univariable and multivariable logistic regression. Patients diagnosed between 2010 and 2015 were selected to investigate prognostic factors for lung metastasis by conducting Cox regression. Kaplan–Meier analysis was used to estimate overall survival outcomes.ResultsA total of 10,598 (5.2%) patients with synchronous lung metastasis were diagnosed among 203,138 patients with CRC. The median survival time of patients with lung metastasis was 10.0 months (95% CI 9.6–10.5 months). Older age, unmarried status, uninsured status, poor histological differentiation, more lymphatic metastasis, CEA positivity, liver metastasis, bone metastasis and brain metastasis were lung metastasis risk and prognostic factors. Black patients and those with left colon, rectum, and stage T4 disease were more likely to develop lung metastasis, while patients with right colon cancer and no surgical treatment of the primary tumour had poor survival outcomes.ConclusionThe incidence of lung metastasis in CRC patients was 5.2%. CRC patients with lung metastasis exhibited homogeneous and heterogeneous risk and prognostic factors. These results are helpful for clinical evaluation and individual treatment decision making.