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Risk factors vary in terms of the pattern of lung cancer metastasis and specific metastatic organs. In this study, we retrospectively analyzed the clinical risk factors of tumor metastasis in lung cancer patients and used second‐generation gene sequencing to characterize relevant gene mutations. The risk factors of different metastatic sites of real‐world lung cancer were explored to find the differentially expressed genes and risk factors in different metastatic organs, which laid a foundation for further study on the metastasis patterns and mechanisms of lung cancer. The clinical risk factors of tumor metastasis in 137 lung cancer patients who attended our department from May 2017 to March 2019 were retrospectively analyzed and grouped based on bone metastasis, brain metastasis, other distant metastasis, and no metastasis. Single‐ or multi‐factor logistic regression analysis was performed to analyze the effect of neutrophil/lymphocyte ratio/platelet/lymphocyte ratio/lymphocyte to monocyte ratio on platelets (PLTs) and bone metastasis by combining PLT values, age, pathology type, gender, and smoking history. Based on the presence or absence of bone metastasis, distal metastasis, and PLT values of lung cancer, 39 tissue specimens of primary lung cancer were taken for 773 gene grouping and gene mutation characterization. The tumor mutation load, gene copy number instability, microsatellite instability, and tumor heterogeneity among different groups were analyzed. Age and PLT level were independent risk factors for bone metastasis and distal metastasis, but not for brain metastasis. The RB1 gene was mutated during bone metastasis, and tumor heterogeneity was less in the elevated PLT group. PLT values were an independent risk factor for distant metastases from lung cancer other than the brain. Age has a significant effect on bone metastasis formation. RB1 gene mutation was significantly associated with bone metastasis., Age and platelet level were independent risk factors for bone metastasis and distal bone metastasis, but age and platelet level were not risk factors for brain metastasis. The RB1 gene was mutated during bone metastasis, and tumor heterogeneity was less in the elevated platelet group. Platelet values are an independent risk factor for distant metastases from lung cancer other than the brain. Age has a significant effect on bone metastasis formation. Mutations in the RB1 gene are significantly associated with bone metastasis.

Peritoneal carcinomatosis (pcm) in metastatic pancreatic ductal adenocarcinomas (mpdac) is frequently encountered in day-to-day practice, but rarely addressed in the literature. The objective of the present study was to describe the management and outcome of patients diagnosed with pcm. Data for all consecutive patients with mpdac treated in our centre between 1 January 2014 and 31 August 2015 were analyzed retrospectively. Computed tomography imaging was centrally reviewed by a dedicated radiologist to determine the date of pcm diagnosis. The analysis included 48 patients. Median age in the group was 61 years, and 41 patients had an Eastern Cooperative Oncology Group performance status (ecog ps) of 0&ndash, 1. All patients presented with pcm either synchronously (group 1) or metachronously (group 2). Those groups differed significantly by baseline ecog ps and neutrophil-to-lymphocyte ratio (nlr), with ecog ps being poorer and nlr being higher in group 1. In addition to pcm, the main sites of metastasis were liver (62.5%) and lungs (31.3%). First-line chemotherapy in 36 patients (75%) was folfirinox (fluorouracil&ndash, irinotecan&ndash, leucovorin&ndash, oxaliplatin). The median overall survival for the entire population was 10.81 months [95% confidence interval (ci): 7.16 months to 14.16 months], it was 13.17 months (95% ci: 5.9 months to 15.4 months) for patients treated with folfirinox. Median overall survival was 7.13 months (95% ci: 4.24 months to 10.41 months) for patients in group 1 and 14.34 months (95% ci: 9.79 months to 19.91 months) for patients in group 2, p = 0.1296. Compared with other metastatic sites, synchronous pcm seems to be a poor prognostic factor. It could be more frequently associated with a poor ecog ps and a nlr greater than 5 in this group of patients. In patients with mpdac and pcm, either synchronous or metachronous, folfirinox remains an efficient regimen.

Immune checkpoint inhibitors have revolutionized treatment and outcome of melanoma and many other solid malignancies including non-small cell lung cancer (NSCLC) and renal cell carcinoma (RCC). Unfortunately, only a minority of patients have a long-term benefit, while the remaining demonstrate primary or acquired resistance. Recently, it has been demonstrated that the prevalence of programmed death-ligand 1 (PD-L1) and tumor-infiltrating lymphocytes (TILs) varies based on the anatomical site of metastases. In particular, liver seems to have more immunosuppressive microenvironment while both the presence of lymph nodal disease and lung metastases seem to have the highest prevalence of PD-L1 and TILs. The aim of the present study is to investigate the possible role of site of metastases as a predictive factor for response or resistance to immunotherapy in several types of cancer. In this multicenter retrospective study, we enrolled patients with metastatic NSCLC, melanoma, RCC, urothelial, merkel carcinoma, and colon cancer who received immunotherapy from April 2015 to August 2019. Major clinicopathological parameters were retrieved and correlated with patients&rsquo, survival outcomes in order to assess their prognostic value and build a useful tool to assist in the decision-making process. A total of 291 patients were included in this study. One hundred eighty-seven (64%) patients were male and 104 (36%) female. The tumor histology was squamous NSCLC in 56 (19%) patients, non-squamous NSCLC in 99 (34%) patients, melanoma in 101 (35%) patients, RCC in 28 (10%) patients, and other tumors in the remaining 7 (2%) patients. The number of metastatic sites was 1 in 103 patients (35%), 2 in 104 patients (36%) and 3 in 84 patients (29%). Out of 183 valuable patients, the entity of response was complete response (CR), partial response (PR), stable disease (SD), and progression disease (PD) in 15, 53, 31, and 79 patients, respectively. Using an univariate analysis (UVA), tumor burden (p = 0.0004), the presence of liver (p = 0.0009), bone (p = 0.0016), brain metastases (p &lt, 0.0001), the other metastatic sites (p = 0.0375), the number of metastatic sites (p = 0.0039), the histology (p = 0.0034), the upfront use of immunotherapy (p = 0.0032), and Eastern Cooperative Oncology Group (ECOG) Perfomance status (PS) &ge, 1 (p &lt, 0.0001) were significantly associated with poor overall survival (OS). Using a multivariate analysis (MVA) the presence of liver (p = 0.0105) and brain (p = 0.0026) metastases, the NSCLC diagnosis (p &lt, 0.0001) and the ECOG PS (p &lt, 0.0001) resulted as significant prognostic factors of survival. Regarding the progression free survival (PFS), using a UVA of the tumor burden (p = 0.0004), bone (p = 0.0098) and brain (p = 0.0038) metastases, the presence of other metastatic sites (p = 0.0063), the number of metastatic sites (p = 0.0007), the histology (p = 0.0007), the use of immunotherapy as first line (p = 0.0031), and the ECOG PS &ge, 1 (p &le, 0.0001) were associated with a lower PFS rate. Using an MVA, the presence of brain (p = 0.0088) and liver metastases (p = 0.024) and the ECOG PS (p &lt, 0.0001) resulted as predictors of poor PFS. Our study suggests that the site of metastases could have a role as prognostic and predictive factor in patients treated with immunotherapy. Indeed, regardless of the histology, the presence of liver and brain metastases was associated with a shorter PFS and OS, but these results must be confirmed in further studies. In this context, a deep characterization of microenvironment could be crucial to prepare patients through novel strategies with combination or sequential immunotherapy in order to improve treatment response.

Background The features and survival of stage IV breast cancer patients with different metastatic sites are poorly understood. This study aims to examine the clinicopathological features and survival of stage IV breast cancer patients according to different metastatic sites. Methods Using the Surveillance, Epidemiology, and End Results database, we restricted our study population to stage IV breast cancer patients diagnosed between 2010 to 2015. The clinicopathological features were examined by chi-square tests. Breast cancer-specific survival (BCSS) and overall survival (OS) were compared among patients with different metastatic sites by the Kaplan-Meier method with log-rank test. Univariable and multivariable analyses were also performed using the Cox proportional hazard model to identify statistically significant prognostic factors. Results A total of 18,322 patients were identified for survival analysis. Bone-only metastasis accounted for 39.80% of patients, followed by multiple metastasis (33.07%), lung metastasis (10.94%), liver metastasis (7.34%), other metastasis (7.34%), and brain metastasis (1.51%). The Kaplan-Meier plots showed that patients with bone metastasis had the best survival, while patients with brain metastasis had the worst survival in both BCSS and OS (p Conclusion Stage IV breast cancer patients have different clinicopathological characteristics and survival outcomes according to different metastatic sites. Patients with bone metastasis have the best prognosis, and brain metastasis is the most aggressive subgroup.

Background Up-to-date information on human epidermal growth factor receptor 2 (HER2) status in breast cancer (BC) is important, as expression can vary during the course of the disease, necessitating anti-HER2 therapy adjustments. Repeat biopsies, however, are not always possible. In this feasibility trial we assessed whether 89Zr-trastuzumab PET could support diagnostic understanding and aid clinical decision making, when HER2 status could not be determined by standard work up. Additionally, HER2 status on circulating tumour cells (CTCs) was assessed. Patients and methods 89Zr-trastuzumab PET was performed in patients if disease HER2 status remained unclear after standard work up (bone scan, 18F-FDG PET, CT and if feasible a biopsy). PET result and central pathologic revision of available tumour biopsies were reported to the referring physician. CTC HER2 status prior to PET was evaluated afterwards and therefore not reported. Diagnostic understanding and treatment decision questionnaires were completed by the referring physicians before, directly after and ≥ 3 months after 89Zr-trastuzumab PET. Results Twenty patients were enrolled: 8 with two primary cancers (HER2-positive and HER2-negative BC or BC and non-BC), 7 with metastases inaccessible for biopsy, 4 with prior HER2-positive and -negative metastases and 1 with primary BC with equivocal HER2 status. 89Zr-trastuzumab PET was positive in 12 patients, negative in 7 and equivocal in 1 patient. In 15/20 patients, 89Zr-trastuzumab PET supported treatment decision. The scan altered treatment of 8 patients, increased physicians’ confidence without affecting treatment in 10, and improved physicians’ disease understanding in 18 patients. In 10/20 patients CTCs were detected; 6/10 showed HER2 expression. CTC HER2 status was not correlated to 89Zr-trastuzumab PET result or treatment decision. Conclusion 89Zr-trastuzumab PET supports clinical decision making when HER2 status cannot be determined by standard work up. The impact of CTC HER2 status needs to be further explored. Electronic supplementary material The online version of this article (10.1007/s00259-018-4099-8) contains supplementary material, which is available to authorized users.

Weikai Xiao,1,* Shaoquan Zheng,1,* Anli Yang,2,* Xingcai Zhang,3,* Yutian Zou,1 Hailin Tang,1 Xiaoming Xie1 1Department of Breast Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, People’s Republic of China; 2Department of Medicine; Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; 3Department of Applied Physics, Harvard John A. Paulson School of Engineering and Applied Sciences, Cambridge, MA 02138, USA *These authors contributed equally to this work Background: It was unclear whether breast cancer subtypes are associated with the risk of site-specific metastases. This study aimed to evaluate the relationship between molecular subtypes and distant metastatic sites and their prognostic significance. Methods: We identified 295,213 patients with invasive breast cancer from 2010 to 2014 using the Surveillance, Epidemiology and End Results database. Subtypes were classified into four categories: hormone receptor (HR+)/human epidermal growth factor receptor 2 (HER2−), HR+/HER2+, HR−/HER2+, and triple-negative (HR−/HER2−). Logistic regression was used to assess the association between metastasis location and subtypes. Multivariate Cox models were used to estimate the overall survival (OS) of related factors. Results: According to our study, 3.28%, 1.52%, 1.20%, and 0.35% of newly diagnosed breast cancers presented bone, lung, liver, and brain metastases at diagnosis, respectively. Both metastatic sites and subtypes significantly affected the OS after metastasis. In multivariate analysis, HR+/HER2+ subtype (OR as compared with HR+/HER2− subtype, 1.30 [95% CI, 1.22–1.39]) significantly correlated with elevated bone metastasis risk, whereas HR−/HER2+ did not. Both HER2+ subtypes (HR+/HER2+ and HR−/HER2+) were significantly associated with higher rates of liver, brain, and lung metastases, while the highest OR was observed in liver metastases. Triple-negative tumors had a higher rate of brain (OR, 1.95 [95% CI, 1.61–2.35]), liver (OR, 1.35 [95% CI, 1.20–1.51]), and lung metastases (OR, 1.34 [95% CI, 1.21–1.47]), but a significantly lower rate of bone metastases (OR, 0.64 [95% CI, 0.59–0.69]) than HR+/HER2− tumors. Conclusions: Breast cancer subtypes are associated with different metastatic patterns and confer different prognostic impacts. Molecular subtypes can identify patients at increased risk of site-specific metastases. Keywords: breast cancer, molecular subtypes, metastasis behavior, prognosis, metastatic sites

Breast cancer is a highly heterogeneous disease at the molecular level and >90% of mortalities are due to metastasis and its associated complications. The present study determined the impact of molecular subtypes on metastatic behavior and overall survival (OS) of patients with metastatic breast cancer. The influence of molecular subtypes on the sites and number of metastases in 166 patients with metastatic breast cancer from a single center were assessed; and the influence of molecular subtypes on the sites and number of metastases and OS in 15,322 metastatic cases among 329,770 patients with primary breast cancer from the Surveillance, Epidemiology and End Results database were assessed. Analysis of both datasets revealed that different molecular subtypes exhibited differences in the prevalence of different metastatic sites and number of metastases. A larger proportion of bone metastasis was observed in the hormone receptor (HR)+/human epidermal growth factor receptor 2 (HER2)+ subtype than in other subtypes, more lung metastasis was observed in the HR-/HER2+ subtype and more liver metastasis occurred in the HR+/HER2+ and HR-/HER2+ subtypes. Single-site metastasis was more common for the HR+/HER2− subtype than in other subtypes, while 2–3 sites of metastases were more common for the HR+/HER2+ subtype and ≥4 sites of metastases were more frequent in the HR-/HER2+ and HR-/HER2- subtypes. The mean OS of patients with primary breast cancer in the HR+/HER2− subtype group was the longest (78.5 months), while the HR-/HER2- group had the shortest mean OS (69.1 months). The mean OS of the metastatic HR+/HER2+ group was the longest (46.0 months), while the mean OS of the metastatic HR-/HER2- group was the shortest (18.5 months). In conclusion, the results of the present study suggested that different molecular subtypes of breast cancer have different metastatic behavior, as well as mean OS.

Due to differences in natural history and therapy, clinical trials of patients with advanced pancreatic cancer have recently been subdivided into unresectable locally advanced pancreatic cancer (LAPC) and metastatic disease. We aimed to evaluate prognostic factors in LAPC patients who were treated with first-line chemotherapy and describe patterns of disease progression. Patients with LAPC who initiated first-line palliative chemotherapy, 2001–2011 at the BC Cancer Agency were included. A retrospective chart review was conducted to identify clinicopathologic variables, treatment, and subsequent sites of metastasis. Kaplan–Meier and Cox-regression survival analyses were performed. A total of 244 patients were included in this study. For the majority of patients (94.3%), first-line therapy was single-agent gemcitabine. About 144 (59%) patients developed distant metastatic disease and the most frequent metastatic sites included peritoneum/omentum (42.3%), liver (41%), lungs (13.9%), and distant lymph nodes (9%). Median overall survival (OS) for the entire cohort was 11.7 months (95% CI, 10.6–12.8). Development of distant metastases was associated with significantly inferior survival (HR 3.56, 95% CI 2.57–4.93), as was ECOG 2/3 versus 0/1 (HR 1.69, 95% CI 1.28–2.23), CA 19.9 > 1000 versus ≤1000 (HR 1.59, 95% CI 1.19–2.14) and female gender, (HR 1.57, 95% CI 1.19–2.08). In this population-based study, 41% of LAPC patients treated with first-line chemotherapy died without evidence of distant metastases. Prognostic factors for LAPC were baseline performance status, elevated CA 19.9, gender, and development of distant metastasis. Results highlight the heterogeneity of LAPC and the importance of locoregional tumor control.

Introduction: Differentiated thyroid carcinoma (DTC) is the most common pathological type of thyroid carcinoma, which includes papillary and follicular subtypes. DTC is usually indolent, characterized by good prognosis, and long-term survival. Total thyroidectomy is the mainstay of treatment in DTC which is followed by diagnostic whole body 131I (WBI) scan. Like other primary malignancies of the head and neck, DTC follows a consistent pattern of spread in the cervical LNs. The central compartment, level VI and VII, is the first sentinel node followed by spread to the lateral compartments levels II–V, followed by the contralateral side. Inspite of nodal involvement, DTC usually have a favourable outcome. Presence of extrapulmonary distant metastases could predict a poor prognosis for high-dose 131I therapy. However, distant metastasis occurs often as a grave event and mortality rates vary depending on metastatic sites. Aim and Objectives: A range of rare 131I concentrating DTC deposits in sella, orbit, choroid, skeletal muscles, liver, skin, costochondral soft tissue, pancreas and kidney, and a few benign 131I concentrating sites are being depicted. Materials and Methods: Metastatic sites from DTC can be easily identified by performing a whole body 131I (WBI) scan along with a stimulated thyroglobulin (Tg) estimation (TSH >30 uIU/ml). Apart from thyroid and thyroid-related diseases, certain benign non-thyroidal pathologies can concentrate radioiodine (131I). From 13,000 of our patients who underwent radioiodine scan for thyroid cancer, we have selected a few cases of 131I concentrating benign and malignant lesions for illustration. Results: Out of 13000 DTC patients who underwent whole body 131I scintigraphy in our department from Jan 2007 till Mar 2018, 25 patients revealed benign sites of 131I uptake. 61 % patients had residual thyroid tissue with or without associated nodal involvement. Remaining patients had distant metastases. Rare sites of functioning thyroid metastases and benign sites of I 131 uptake have been selected for illustration. Conclusion: Apart from the WBI (two-dimensional, planar) images, single-photon emission computed tomography-computed tomography (SPECT-CT) has been incremental in localizing benign lesions which greatly depends on their location. This pictorial review highlights the need to create an awareness to detect metastatic deposits of DTC at unexpected sites. Otherwise patients will need further investigation to rule out unsuspected sites of functioning distant metastases.

Monoclonal antibodies (mAbs) have been approved for use as diagnostics and therapeutics in a broad range of medical indications, but especially in oncology. In addition, hundreds of new mAbs, engineered mAb fragments, and nontraditional antibody-like scaffolds directed against either validated or novel tumor targets are under development. Immuno positron emission tomography (PET), the tracking and quantification of mAbs with PET in vivo, is an exciting novel option to improve diagnostic imaging and to guide mAb-based therapy. In this review, recent technical advances leading to a jump ahead in mAb imaging are discussed. The availability of proper positron emitters, sophisticated radiochemistry, and advanced PET and PET-computed tomography scanners is crucial in these developments. Immuno-PET might play an important future role in cancer staging, in the improvement and tailoring of therapy with existing mAbs, and in the efficient development of novel mAbs. An overview of the preclinical and first clinical immuno-PET studies is provided.

Breast cancer affects approximately 12 % women worldwide and results in 14 % of all cancer-related fatalities. Breast cancer is commonly categorized into one of four main subtypes (luminal A, luminal B, human epidermal growth factor receptor 2 (HER2) positive and basal), indicating molecular characteristics and informing treatment regimes. The most severe form of breast cancer is metastasis, when the tumour spreads from the breast tissue to other parts of the body. Significantly, the primary tumour subtype affects rates and sites of metastasis. Currently, up to 5 % of patients present with incurable metastasis, with an additional 10-15 % of patients going on to develop metastasis within 3 years of diagnosis. MicroRNAs (miRNAs) are short 21-25 long nucleotides that have been shown to significantly affect gene expression. Currently, > 2000 miRNAs have been identified and significantly, specific miRNAs have been found associated with diseases states. Importantly, miRNAs are found circulating in the blood, presenting an opportunity to use these circulating disease-related miRNAs as biomarkers. Clearly, the identification of circulating miRNA specific to metastatic breast cancer presents a unique opportunity for early disease identification and for monitoring disease burden. Currently however, few groups have identified miRNA associated with metastatic breast cancer. Here, we review the literature surrounding the identification of metastatic miRNA in breast cancer patients, highlighting key areas where miRNA biomarker discovery could be beneficial, identifying key concepts, recognizing critical areas requiring further research and discussing potential problems.

Metastatic disease occurs in a significant percentage of patients with renal cell carcinoma (RCC) and is usually associated with an overall poor prognosis. However, not all of the sites of metastases seem to have the same prognostic significance in patients receiving targeted agents. Indeed, patients with lung-only metastases seem to present a better survival than patients with other sites, whereas liver and bone metastases are associated with a worst prognosis. Some clinical studies suggest that metastatic sites are more responsive than primary tumors. This event may be due to intratumor heterogeneity in terms of somatic mutations, chromosome aberrations, and tumor gene expression, primarily centered around Von Hippel–Lindau (VHL) pathway, such as VHL mutations, HIF levels, vascular endothelial growth factor (VEGF) isoforms, and VEGF receptor levels. Nevertheless, these data do not completely explain the discordant biological behavior between primary tumor and metastatic sites. Understanding the causes of this discordance will have profound consequences on translational research and clinical trials in RCC. In this review, we overview current data on the differences between primary RCC and metastases in terms of drug target expression and clinical/radiological response to targeted agents, thus describing the prognostic role of different metastatic sites in RCC patients.