Single Organ Metastasis Research Articles

Initial Impact of National CRC Screening on Incidence and Advanced Colorectal Cancer

Screening for colorectal cancer (CRC) aims to decrease CRC incidence and mortality. Biennial fecal immunochemical test screening started in the Netherlands in 2014 for individuals 55-75 years of age. This study investigated the effect of screening on stage-specific incidence, with focus on stage III and IV CRC. Inhabitants diagnosed with CRC in 2009-2018 were included. CRC incidence per stage, year, and detection method (ie, screen-detected vs clinically detected) was evaluated. Patient, tumor, and treatment characteristics, and survival of patients with stage III and IV CRC, were compared according to the detection method. Included were 140,649 CRCs in 136,882 patients. An initial peak of stage I-III CRC diagnoses after initiation of screening was followed by a continuous decrease within screening-eligible ages. Total CRC incidence remained higher than before screening, although stage II and IV CRC incidence decreased below prescreening levels. Screen-detected CRCs were significantly more frequently located in the left-sided colon (stage III; 43.7% vs 30.9%; stage IV: 45.1% vs 36.1%), and the primary tumor resection rate was higher (stage III colon: 99.8% vs 99.0%, rectum: 97.3% vs 89.7%; stage IV colon: 65.4% vs 56.6%, rectum: 47.3% vs 33.5%). Patients with screen-detected stage IV CRC had significantly more often single-organ metastases (74.5% vs 57.0%; P < .001) and more frequently received treatment with curative intent (colon: 41.3% vs 27.4%; rectum: 33.8% vs 24.6%). Overall survival significantly improved for patients with screen-detected CRCs (stage III: P < .001; stage IV: P < .001). Five years after the start of a nationwide CRC screening program, a decrease in stage II and IV CRC incidence was observed. Patients with screen-detected stage III and stage IV CRC had less extensive disease and improved survival compared with those with clinically detected CRC.

Exploring the Value of Additional Primary Tumour Excision Combined with Systemic Therapy Administered in Different Sequences for Patients with de Novo Metastatic Breast Cancer

Introduction Uncertainty still remains regarding the survival improvement derived from immediate surgery or subsequent surgery in addition to systemic therapy for patients with de novo metastatic breast cancer. The current study aimed to examine the effect of combined treatment administered in different sequences on the survival of these patients. Materials and Methods We conducted a retrospective cohort study of patients with de novo stage IV breast cancer in the Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2019. Patients were categorized into 3 groups: (1) systemic therapy without primary surgery, (2) systemic therapy after primary surgery, and (3) systemic therapy before primary surgery. Cumulative incidence curves with Gray's test were used to compare breast cancer-specific death (BCSD) between groups. Kaplan–Meier curves with the log-rank test were applied to compare overall survival (OS) between groups. A competing risk model and a proportional hazards model were generated to adjust for important prognostic factors. Propensity score matching (PSM) was performed in the primary survival analysis. Stratified analysis was also performed. Results Patients who underwent systemic therapy after primary surgery and who underwent systemic therapy before primary surgery both showed a significantly reduced risk of BCSD compared to patients who received systemic therapy without primary surgery [subdistribution hazard ratio (SHR): 0.74; 95% confidence interval (CI): 0.69–0.79; and P < 0.001, and SHR: 0.62; 95% CI: 0.56–0.67; and P < 0.001, respectively]. A statistically significant disparity was also noted in OS. In the setting of single-organ metastasis, including the bone, lung, and liver, patients receiving the combination therapy showed an improved prognosis compared with patients receiving systemic therapy without primary surgery. Conclusions Additional primary tumour excision, whether before or after systemic therapy, may provide survival benefits for patients presenting with de novo metastatic breast cancer, especially for patients with single-organ disease involving the bone, lung, and liver but not the brain. Further investigations mainly focused on these carefully selected candidates are required to improve personalized treatment for metastatic breast cancer.

Metastatic site-specific prognosis of women with stage IVB cervical cancer (345)

Objectives: In patients with cervical cancer, evidence of tumor spread to organs distant from the uterine cervix is indicative of stage IVB disease. Despite the heterogeneity of anatomical sites that tumor may affect, stage IVB encompasses all distant metastasis within the current cancer staging schematic. This study examined survival outcomes based on metastasis sites of cervical cancer metastasis. Methods: This retrospective observational cohort study utilized the National Cancer Institute’s Surveillance, Epidemiology, and End Result Program from 2010-2018. The study population included 1,772 women with stage IVB cervical cancer who had cervical cancer metastasis to one or more of the following four organs: bone, brain, liver, or lung. Overall survival was assessed based on the metastatic extent in multivariable analysis. Results: The most common metastatic site was lung (n=1210, 68.3%) followed by bone (n=623,35.2%), liver (n=531, 30.0%), and brain (n=21, 1.2%). Multiple organ metastases were seen in 470 (26.5%) women with liver/lung metastases being the most frequent pattern (n=170, 9.6%), followed by bone/lung (n=166, 9.4%) and bone/liver (n=113, 6.4%). A total of 1,442 (81.4%) deaths occurred during the follow-up period. The cohort-level median overall survival was seven months, ranging from three months in all four organ metastases to 11 months in bone metastasis alone when stratified (absolute difference eight months, p<0.001). In multivariable analysis, multiple organ metastases were independently associated with 50% increased all-cause mortality risk compared to single organ metastasis (adjusted HR: 1.50, 95% CI: 1.33-1.69). Conclusions: Survival outcomes in those with stage IVB cervical cancer can vary based upon the extent of metastasis. Incorporating single versus multiple distant organ metastasis into the cancer staging schema may be useful (IVB1 vs IVB2). Objectives: In patients with cervical cancer, evidence of tumor spread to organs distant from the uterine cervix is indicative of stage IVB disease. Despite the heterogeneity of anatomical sites that tumor may affect, stage IVB encompasses all distant metastasis within the current cancer staging schematic. This study examined survival outcomes based on metastasis sites of cervical cancer metastasis. Methods: This retrospective observational cohort study utilized the National Cancer Institute’s Surveillance, Epidemiology, and End Result Program from 2010-2018. The study population included 1,772 women with stage IVB cervical cancer who had cervical cancer metastasis to one or more of the following four organs: bone, brain, liver, or lung. Overall survival was assessed based on the metastatic extent in multivariable analysis. Results: The most common metastatic site was lung (n=1210, 68.3%) followed by bone (n=623,35.2%), liver (n=531, 30.0%), and brain (n=21, 1.2%). Multiple organ metastases were seen in 470 (26.5%) women with liver/lung metastases being the most frequent pattern (n=170, 9.6%), followed by bone/lung (n=166, 9.4%) and bone/liver (n=113, 6.4%). A total of 1,442 (81.4%) deaths occurred during the follow-up period. The cohort-level median overall survival was seven months, ranging from three months in all four organ metastases to 11 months in bone metastasis alone when stratified (absolute difference eight months, p<0.001). In multivariable analysis, multiple organ metastases were independently associated with 50% increased all-cause mortality risk compared to single organ metastasis (adjusted HR: 1.50, 95% CI: 1.33-1.69). Conclusions: Survival outcomes in those with stage IVB cervical cancer can vary based upon the extent of metastasis. Incorporating single versus multiple distant organ metastasis into the cancer staging schema may be useful (IVB1 vs IVB2).

P-195 A cohort of patients (pt) with HER2-positive (HER2+) advanced gastroesophageal cancer (aGEC) treated at our institution after a decade of tailored targeted therapy

aGEC is a dismal prognosis disease with limited treatment options. Molecular characterization of these tumors revealed 15-20% of HER2+ assessed either by immunohistochemistry (IHC 3+) or by fluorescence in situ hybridization (FISH amplified/IHC 2+). Since 2010, the TOGA trial established a combination of chemotherapy (CHT) plus trastuzumab (TTZ), a specific antiHER2 mAb, as the standard of care (SoC) in first line for HER2+ aGEC pt. After a decade of implementing this personalized therapy, we aim to describe the clinic-pathological characteristics and outcomes of the subset of HER2+ aGEC pt treated at our Institution. We performed a descriptive analysis of 29 pt diagnosed with HER2+ aGEC treated with CHT plus TTZ at Catalan Institute of Oncology, Badalona, from 2016 to 2021. For the purposes of this study, pt enrolled in clinical trials were excluded. Data regarding demographic and cancer characteristics, treatment and survival outcomes were collected retrospectively from available electronic medical records. Data analysis was performed using SPSS program. Median age was 61 years (29-78) and 90% of pt were men. Regarding primary location, 42% were gastroesophageal junction (GEJ), 34% gastric and 24% were distal esophagus tumors. All tumors were adenocarcinomas. HER2 status was reported as IHC 3+ in 23 pt, whilst 6 pt were IHC 2+, in which FISH resulted amplified in all cases. Metastatic disease was present in 22 pt at diagnosis, and the other 7 pt were initially staged as locally advanced disease before progressing into advanced disease. Most common metastatic sites were hepatic (18%), peritoneal (14%) or a combination of different locations (59%). Only 2 pt (9%) had single organ metastasis in a different location from the previously described (adenopathy and lung). All pt were treated with a platinum and fluoropirimidine-based CHT plus TTZ SoC. Median progression-free survival (PFS) following first line was 8.4 months (m) [(95% confidence interval (CI) 5.4-11.4]. Median overall survival (OS) was 14.63 m [95% CI 5.7-23.6]. To date, 25 pt were deceased, but one pt is still receiving CHT plus TTZ as first line. Noteworthy, 2 pt outliers who achieved complete response to CHT plus TTZ are currently under surveillance without specific cancer treatment. Second line treatment was feasible in 13 pt, 4 pt received a further third line and even 1 pt was able to receive a fourth line. The TTZ-based therapy has significantly improved the outcomes for HER2+ aGEC pt, as illustrated by OS>12m and 50% pt receiving alternative treatment beyond first line. Survival outcomes observed in our cohort were consistent with previously described outcomes available in the literature. Deeper characterization of the outliers is warranted to shed more light into the molecular determinants that predict efficacy. Furthermore, translational efforts to identify resistance mechanisms to TTZ are mandatory to guide future personalized strategies in this subset of HER2+ aGEC.

Metastatic extent-specific prognosis of women with stage IVB cervical cancer: multiple versus single distant organ involvement.

Despite the heterogeneity of anatomical sites that metastases may affect, within the current cancer staging schematic, stage IVB encompasses all distant metastasis. This study examined survival outcomes based on the extent of distant organ metastasis in stage IVB cervical cancer. This retrospective cohort study utilized the National Cancer Institute's Surveillance, Epidemiology, and End Result Program from 2010 to 2018. The study population included 1772 women with stage IVB cervical cancer who had tumor metastasis to one or more of the following four organs: bone, brain, liver, or lung. Overall survival was assessed based on the metastatic extent in multivariable analysis. The most common metastatic site was lung (68.3%) followed by bone (35.2%), liver (30.0%), and brain (1.2%). Multiple organ metastases were seen in 26.5% of study population, with lung/liver metastases being the most frequent combination pattern (9.6%) followed by lung/bone (9.4%), and lung/bone/liver (6.4%). A total of 1442 (81.4%) deaths occurredduring the follow-up. The cohort-level median overall survival was 7months, ranging from 3months in all four organ metastases to 11months in bone metastasis alone when stratified (absolute difference 8months, P < 0.001). Multiple organ metastases were independently associated with nearly50% increased all-cause mortality risk compared to single organ metastasis (adjusted-hazard ratio 1.51, 95% CI 1.34-1.70). Survival outcomes in those with stage IVB cervical cancer with distant organ involvement can vary based on the extent of metastasis. Incorporation of single versus multiple distant organ metastasis into the cancer staging schema may be valuable (IVB1 versus IVB2).

Prognostic usefulness of clinical features and pretreatment 18F-FDG PET/CT metabolic parameters in patients with angiosarcoma.

To investigate the prognostic value of clinical features and metabolic parameters in pretreatment 18F-2-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography/X-ray computed tomography (PET/CT) scans of patients with angiosarcoma, a rare neoplasm that has not been well characterized. In this retrospective study, 19 patients with a histopathologically confirmed diagnosis of angiosarcoma who had undergone pretreatment 18F-FDG PET/CT scans were enrolled. We recorded the age at presentation, sex, underlying diseases, sites of primary tumors, Karnofsky Performance Status (KPS) score, Eastern Cooperative Oncology Group (ECOG) score, time from onset to diagnosis, laboratory examinations, sites and sizes of primary tumors, treatment modalities, histologic features and American Joint Committee on Cancer (AJCC) stage, maximum standardized uptake value (SUVmax), average SUV (SUVavg), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of primary tumors and the whole body. Univariate and multivariate survival analyses for overall survival were performed according to the metabolic parameters and other clinical variables. Patients ranged in age from 27 to 79 years (median: 59 years) with different angiosarcoma types covering all tumor grades and subtypes. Seven (7/19) patients had anemia of varying degrees of severity. Lymph node metastases (n=10) and/or distant metastases (n=11) of angiosarcoma were common. Bone or bone marrow (10/19) and lung (8/19) were the most common distant metastatic organs. Patients with bone metastases, low hemoglobin levels and high ferritin levels had significantly poorer overall survival than those with non-bone metastases, normal hemoglobin levels and normal ferritin levels by the log-rank test, with P values of 0.027, 0.030 and 0.015, respectively. Patients with multiple organ metastases had significantly poorer overall survival than those with single organ metastasis (log-rank P=0.008). In multivariate survival analysis, only whole-body metabolic tumor volume using SUVmax cut-off value of 2.5 (wMTV2.5) was a significant independent prognostic factor. For wMTV2.5, 870.3 cm3 was the best cut-off point to discriminate between a good and poor prognosis (log-rank P=0.01). The systemic 18F-FDG PET/CT with high sensitivity and specificity has significant advantages in the evaluation of angiosarcoma, particularly in detecting occult metastases. Bone metastases on 18F-FDG PET/CT, low hemoglobin levels and high ferritin levels were all associated with a poorer prognosis. MTV2.5 of the whole body is a significant independent metabolic prognostic factor for overall survival in patients with angiosarcoma.

Effects of Metastatic Sites on Circulating Tumor DNA in Patients With Metastatic Colorectal Cancer

Low concordance between plasma-based and tissue-based tests for determining the RAS mutational status have been reported in some but not all patients with limited-extent metastatic colorectal cancer (mCRC). In this study, we investigated the relationship between metastatic site and circulating tumor DNA (ctDNA) detection using ctDNA genotyping, an alternative to tissue genotyping for precision oncology. We investigated the relationship between metastatic site and ctDNA detection using Guardant360, a next-generation sequencing ctDNA assay, in mCRC patients with single-organ metastasis in the SCRUM-Japan GOZILA study (UMIN000029315). Of 1,187 patients with mCRC enrolled in GOZILA, 138 were eligible (49 with liver-only, 15 with lymph node-only, 27 with peritoneum-only, and 47 with lung-only metastases). The concordance of RAS/BRAF status between Guaradant360 and tissue in vitro diagnostic tests was 95.9% in patients with liver-only, 80.0% in lymph node-only, 56.0% in peritoneum-only, and 65.9% in lung-only metastases. ctDNA fraction, as measured by the median maximum variant allelic fraction (max VAF), and median number of detected variants were 23.1% and five in liver-only, 6.0% and five in lymph node-only, 0.4% and three in peritoneum-only, and 0.4% and three in lung-only metastases, respectively (all P < .001, Kruskal-Wallis test). Few patients with liver-only (2.0%) and lymph node-only metastasis (13.3%) had a max VAF < 0.2%, which is required to ensure a detection limit of 95%, but max VAF was more frequently < 0.2% in patients with lung-only (27.7%) or peritoneum-only metastasis (29.6%). Patients with lung-only and peritoneum-only metastatic disease have significantly lower levels of ctDNA, suggesting decreased clinical sensitivity for subclonal variants. This observation suggests that such patients may benefit from concurrent tissue and plasma testing to provide optimal genotyping for subsequent therapy selection.

Patterns of metastasis and prognosis of elderly esophageal squamous cell carcinoma patients in stage IVB: a population-based study.

BackgroundEsophageal squamous cell carcinoma (ESCC) has been listed among the most common esophageal cancers (ECs). Patients are generally relatively old in terms of their age at diagnosis of ESCC. A retrospective, population-based study appraising 537 elderly ESCC patients who suffered distant metastasis (DM) in stage IVB from 2010 to 2016 was performed. To this end, data pertaining to Surveillance, Epidemiology, and End Results (SEER) were adopted.MethodsA total of 537 elderly patients with IVB-stage ESCC suffering DM treated from 2010 to 2016 were taken as subjects. Prognosis was determined by using Kaplan-Meier analysis, as well as univariate and multivariate Cox regression. In accordance with sites of metastasis, these patients were classified into five groups: bone-, lung-, brain-, liver-only, and multiple-site (metastases to two or more organs) groups. In order to assess the prognosis, the cancer-specific survival (CSS), median survival time (MST), overall survival (OS), and survival rate (SR) were examined.ResultsThe lung was found to be the organ most vulnerable to metastasis in the population with single-organ metastasis, and liver, bone and brain followed in descending rank order. Relative to the group only having bone metastasis, the multiple-site group had the lowest CSS (HR: 1.067; 95% CI: 0.767–1.485; P=0.700) and OS (HR: 1.051; 95% CI: 0.759–1.454; P=0.766). The MST (MST: both 2 months in CSS and OS) and SR (6-month SR: 28.2% in CSS, 27.7% in OS; 1-year SR: 7.5% in CSS, 6.7% in OS; 3-year SR: 2.5% in CSS, 1.5% in OS) were also found to be the lowest for the multiple-site group among the total population. These patients benefited from treatment with chemotherapy (C), radiotherapy (R), and surgery (S), as evinced by the prognosis (CSS and OS: P<0.001), in comparisons with untreated patients (N) in the total population. The S or/and R + C resulted in no statistically significant differences to C alone (CSS: P=0.593; OS: P=0.510) in terms of the prognostic results, which indicated that C alone can have almost the same prognostic effect as multimodal therapy.ConclusionsPopulation-based research was used to determine patterns of metastasis and survival outcomes of elderly patients with IVB-stage ESCC suffering DM. The worst CSS and OS were found in patients with multiple-site metastasis across all groups. The treatment is an independent prognostic factor affecting prognosis. Chemotherapy plays a vital role in prognosis. Active therapies are beneficial to elderly patients with IVB-stage ESCC suffering DM, particularly chemotherapy.

A Possible Definition of Oligometastasis in Pancreatic Cancer and Associated Survival Outcomes.

Oligometastatic cancer (OM) is possibly associated with relatively better survival outcomes. We attempted to identify cases in line with this OM concept. A total of 130 cases with unresectable metastatic pancreatic cancer underwent non-curative surgery from April 2001 to December 2019. Sites of metastasis, clinicopathological information, and surgical outcomes were collected to formulate a better definition of OM. OM criteria were defined as having metastasis to a single organ, few countable lesions and low serum cancer antigen 19-9 level. The median overall survival after non-curative surgery of OM cases was 13.0 months and was significantly better than that of non-OM cases (8.4 months, p=0.003). We propose single-organ metastasis of limited tumor volume (H1 or P1/2 by the Japanese Society of Cancer of the Colon and Rectum classification) and low serum cancer antigen 19-9 level (<2,000 U/ml) as new criteria for defining OM pancreatic cancer.

Lobectomy Can Improve the Survival of Patients With Non-small Cell Lung Cancer With Lung Oligometastatic.

Background: This study was to evaluate the value of lobectomy in the prognosis of Non-small cell lung cancer (NSCLC) patients with primary metastasis based on the Surveillance Epidemiology and End Results (SEER) database.Methods: This was a population-based retrospective study and the clinical data were collected from the National Cancer Institute's SEER database between 2010 and 2015. The effects of pulmonary surgery and surgical procedures on lung cancer-specific survival (LCSS) and overall survival (OS) were assessed, and the COX regression models were employed to evaluate the survival of primary surgery in patients with primary metastatic NSCLC (pmNSCLC) and the survival of surgical procedure in pmNSCLC patients.Results: A total of 55,717 patients diagnosed with pmNSCLC between 2010 and 2015 were enrolled, and pulmonary surgery was indicated in 1,575 (2.83%) patients. Surgery was an independent risk factor for LCSS (P < 0.001, HR 0.658, 95%CI: 0.637–0.680) and OS (P < 0.001, HR 0.665, 95%CI: 0.644–0.686) of pmNSCLC patients. The surgery was associated with better OS (P < 0.001, HR 0.678, 95%CI: 0.657–0.699). The site of metastasis was also related to the survival after primary tumor surgery (P = 0.001). As compared to the sublobectomy and pneumonectomy, lobectomy improved the LCSS for NSCLC patients with single-organ metastasis, rather than multiple metastases (P < 0.001). In patients receiving sublobectomy, lobectomy, and pneumonectomy, the median LCSS was 12, 28, and 13 months, respectively, and the 5-year LCSS rate was 14.39, 32.06, and 17.24%, respectively.Conclusion: The effect of locoregional surgery on the survival of pmNSCLC patients with single-organ metastasis has been underestimated, and lobectomy may be a preferred treatment for patients with single-lung metastasis.

The association between molecular type and prognosis of patients with stage IV breast cancer: an observational study based on SEER database.

Molecular subtype, the basis for personalized treatment of breast cancer, is of great value in evaluating prognosis and guiding treatment of early-stage breast cancer. However, its value in stage IV patients remains unclear. In this study, we investigated the association between molecular subtype and prognosis of de novo stage IV breast cancer using Surveillance, Epidemiology, and End Results (SEER) database with the purpose to provide evidence for optimal therapeutic options for breast cancer patients. We retrospectively analyzed de novo stage IV breast cancer patients with the SEER Program data from 2010 to 2015. Characteristics of patients with different molecular subtypes were compared by chi-square test and survival curves for breast cancer specific survival (BCSS) according to subtypes were plotted by Kaplan-Meier method. The Cox proportional hazards model was performed to search for independent prognostic factors in stage IV breast cancer patients. A total of 11,974 patients were included in this study, among which 7,100 (59.30%) patients were of HR+/HER2-, 2,093 (17.48%) of HR+/HER2+, 1,139 (9.51%) of HR-/HER2+ and 1,642 (13.71%) of HR-/HER2-. Multivariate Cox analysis revealed that molecular subtype, age, race, marital status, grade, surgery and chemotherapy were independent prognostic factors for BCSS in de novo stage IV patients. Taking HR+/HER2- patients as reference, HR+/HER2+ patients had better BCSS (HR =0.81, 95% CI: 0.75-0.88, P<0.001), HR-/ HER2- patients had worse BCSS (HR =1.42, 95% CI: 1.29-1.46, P<0.001) and HR-/HER2+ patients had no significant difference (HR =1.03, 95% CI: 0.98-1.08, P=0.188). In patients with different single organ metastases, the prognosis of HR+/HER2+ subtype was the best (except brain metastasis), while that of HR-/HER2- subtype was the worst. Molecular subtypes were closely associated with the prognosis of de novo stage IV breast cancer. Among the four subtypes, HR+/HER2+ patients had the best prognosis while HR-/HER2- patients had the worst. The prognosis of patients with different single organ metastases was the same, but in patients with brain metastases, HR+/HER2+ ones did not have a significantly better prognosis than other subtypes except triple-negative type.

Metastasis Patterns and Prognosis of Elderly Patients With Esophageal Adenocarcinoma in Stage IVB: A Population-Based Study.

BackgroundEsophageal adenocarcinoma (EAC) is the most common kind of esophageal cancer. Age at diagnosis of advanced EAC is greater. Studies about practice patterns for elderly EAC patients with distant metastasis (DM) in stage IVB are limited. This retrospective, population-based study was conducted using data from the Surveillance, Epidemiology, and End Results (SEER) to evaluate 855 elderly EAC patients with DM in stage IVB from 2010 to 2015.Methods855 elderly EAC patients with DM in stage IVB between 2010 and 2015 were included in this study. Univariate and multivariate Cox-regression and Kaplan-Meier analyses were used to assess prognosis. These patients were classified to bone-only, brain-only, lung-only, liver-only, and multiple (patients with two or more organs in metastasis)-site group according to the site of metastasis. Overall survival (OS), cancer-specific survival (CSS), median survival time (MST), and survival rate (SR) were evaluated to analyze the survival outcomes.ResultsThe most common metastasis site was the liver among the single-organ metastasis population, followed by lung, bone, and brain. Compared with the bone-only group, the multiple-site group was associated with worst OS (HR: 1.037, 95% CI: 0.811–1.327, p = 0.770) and CSS (HR: 1.052, 95% CI: 0.816–1.357, p = 0.695). The multiple-site group also had the lowest MST in the population (MST: 2 months in OS and 3 months in CSS) and SR (6-month SR: 27.1% in OS, 29.9% in CSS, 1-year SR: 10.7% in OS, 12.0% in CSS, 3-year SR: 2.5% in OS, 2.8% in CSS). Compared to untreated patients (N) in the total population, other patients who were treated with surgery (S), radiotherapy (R), and chemotherapy (C) are beneficial for the prognosis (OS and CSS: p < 0.001).ConclusionThis population-based study was conducted to ascertain metastasis patterns and survival outcomes of EAC patients with DM in stage IVB. Elderly patients with multiple-site metastasis exhibited the worst OS and CSS among all the populations, and patients with bone-only metastasis had the worst OS and CSS among single-organ metastasis populations. Active treatment is beneficial for elderly EAC patients with DM in stage IVB, especially chemotherapy. This study also shows that more than one third of the patients had not received any therapy.

Hyper engorged cancer associated macrophage-like cells in circulation predict for multi-organ metastatic disease in solid tumors.

3039 Background: Patients with multiple organ metastases have poorer prognoses than those with a single organ metastasis, are frequently associated with drug resistance, and have higher tumor burden. Engorged (≥50um) Cancer Associated Macrophage-Like Cells (CAMLs) are a circulating stromal cell subtype detected in the blood of patients with solid tumors at high risk for recurrence or progression. While numerous studies have shown that ≥50um CAMLs predict poor clinical outcomes, meta-analysis of these studies have also suggested that hyper engorged CAMLs ≥100um (heCAMLs) may be associated with multifocal metastatic disease and even worse outcomes. In this prospective study, we evaluated the presence of heCAMLs in patients with metastatic disease and demonstrated a strong relationship with multi organ spread, which also correlated with shorter Progression Free Survival (PFS) and Overall Survival (OS). Methods: We prospectively recruited 151 patients with metastatic (m) mbreast (n = 58), mlung (n = 34), mprostate (n = 39), and mrenal (n = 20) cancers. Peripheral blood was collected prior to the induction of new treatment for metastatic cancer. Cells were isolated following standard CellSieve techniques, then imaged and measured in ZenBlue. Multi organ metastasis was defined as spread to ≥2 distant organ sites, or any spread to the brain. Single factor ANOVA was conducted to compare heCAML presence in multi organ metastatic patients versus patients with single organ site metastasis. Univariate and multivariate analysis was run to evaluate for PFS and OS against heCAMLs, and all known clinical parameters. Results: 150 viable samples (excluding 1 failed sample) were obtained. Multi organ metastases were present in 55% (n = 83/150) of patients. heCAMLs were found in 59% (n = 49/83) of the multi organ metastatic population, but only in 16% (n = 11/67) of the single site metastatic cohort (p &lt; 0.001). heCAML presence appeared to differentiate multi organ vs single organ metastases in mbreast (85% vs. 52%, p = 0.006), mlung (71% vs. 26%, p = 0.025), mprostate (75% vs. 37%, p = 0.029), and mRCC (88% vs. 36%, p = 0.025). Further, in all n = 150 patients, heCAML presence predicted a significantly shorter median PFS of 4.5 versus 7.2 months, 24 month PFS (HR = 1.67, 95%CI = 1.13-2.45, p = 0.013), and significantly shorter median OS of 13.1 versus 20.4 months, 24 month OS (HR = 2.05, 95%CI = 1.24-3.39, p = 0.008). Conclusions: We examined a non-invasive prognostic blood based assay to determine its relationship to multi organ metastatic spread as well as its prognostic value in several solid cancers. These results showed patients with heCAMLs had higher rates of multi organ metastases, and appear to predict for shorter PFS and OS. Studies of larger cohorts are needed for prospective validation of these initial findings.

The impact of colorectal cancer screening on incidence and stage IV disease in the Netherlands.

3531 Background: Population-based screening for colorectal cancer (CRC) aims to decrease incidence and mortality due to precancerous polyp removal, early detection and early treatment of CRC. In the Netherlands, phased introduction of a biennial fecal immunochemical hemoglobin test started in 2014 for individuals aged 55-75. This evaluation of the national data focuses on the initial effect of CRC screening on incidence and stage distribution and the impact on stage IV disease. Methods: All CRC patients diagnosed in the Netherlands between 2009 and 2018 were selected from the Netherlands Cancer Registry (NCR). Patients were linked to the Dutch national pathology registry (PALGA) to identify screen-detected tumors. Results: The NCR identified 137,717 CRC patients between 2009 and 2018. The incidence within screening age (55-75 yr) of all CRC stages showed an initial peak after introduction of screening in 2014, followed by a continuous decrease for all stages. CRC incidence outside the screening age did not show these explicit changes between 2009 and 2018. In 2018, the incidence of stage IV CRC within screening age was lower than the level at the start of the screening program. Stage distribution within screening age shifted towards earlier stages in the screening period (2014-2018) compared to the period before screening (2009-2012) (stage I: 31% vs. 18%, stage II: 22% vs. 26%, stage III: 29% vs. 31%, Stage IV: 18% vs. 25%, respectively). In the period 2014-2018 and within screening age, the ratio of screen-detected and symptom-detected tumors was highest in stage I (47%:53%) and lowest in stage IV (9%:91%). Screen-detected compared to symptom-detected stage IV patients diagnosed in the period 2014-2018 and within screening age had more frequently single organ metastases (74.5% vs 57.4%, p &lt; 0.001), higher resection rate of the primary tumor (57.5% vs. 41.3%; p &lt; 0.001) and higher local treatment rate of metastases (40.0% vs. 23.4% p &lt; 0.001). The median overall survival of screen-detected stage IV patients was significantly longer than that of symptom-detected stage IV patients (31.0 months (95% CI: 27.7 – 34.3) vs. 15.0 months (95% CI: 14.5 – 15.5), p &lt; 0.001). Conclusions: The initial results of the introduction of CRC screening in the Netherlands showed a favorable trend on CRC incidence and stage distribution. Screen-detected patients with stage IV disease had less extensive disease, resulting in better treatment options and improved survival.

Correlation and Survival Analysis of Distant Metastasis Site and Prognosis in Patients With Hepatocellular Carcinoma.

PurposeTo investigate the prognostic factors and survival analysis of patients with hepatocellular carcinoma with distant metastasis.MethodsThe clinical data of 3,126 patients with distant metastasis of hepatocellular carcinoma from 2010 to 2015 were extracted from SEER database, and the correlation between the location of distant metastasis of hepatocellular carcinoma and prognosis was retrospectively analyzed. Patients were grouped according to different metastatic sites. The clinical characteristics of each group were compared by chi-square test, the survival curve was drawn by Kaplan-Meier method, Log-rank test was used for univariate analysis, and Cox regression for multivariate analysis. And use propensity score matching (PSM) to reduce differences in baseline characteristics.ResultsBefore PSM, the prognosis of patients with hepatocellular carcinoma with lung metastasis is worse than that of patients without lung metastasis. And there was no statistically significant difference with or without bone metastases.Patients with one type of organ metastasis had better prognosis than those with multiple organ metastasis. Among patients with organ metastasis, bone metastasis has a better prognosis than patients with lung metastasis. After PSM, patients with HCC with bone metastases had a worse prognosis than those without bone metastases (P<0.05). Univariate analysis showed that the degree of tumor differentiation, T stage, N stage, primary tumor and metastatic surgery, radiotherapy and chemotherapy, tumor size, single organ metastasis, the number of metastatic organs, and the combination of metastatic organs were related to the prognosis of patients with distant metastasis of hepatocellular carcinoma (P < 0.05). Multiariate analysis showed that age ≥52 years old, male, low degree of tumor differentiation, N1 stage, no primary surgery, no chemoradiotherapy, tumor size > 6cm, and multi-organ metastasis were independent influencing factors for poor prognosis in patients with metastatic hepatocellular carcinoma.ConclusionThe lung is the most common site of distant metastasis of hepatocellular carcinoma. Single organ metastasis has better prognosis than multiple organ metastasis. Age ≥52 years old, male, low degree of tumor differentiation, N1 stage, no primary surgery, no chemoradiotherapy, tumor size > 6cm, and multi-organ metastasis were independent influencing factors for poor overall survival and cancer-specific survival prognosis in patients with metastatic hepatocellular carcinoma.

Sequence for Surgical Resection of Primary Lung Tumor for Oligometastatic Non-small Cell Lung Cancer

BackgroundDiffering surgical series for the treatment of primary lung tumor with synchronous oligometastatic stage IV non-small cell lung cancer (NSCLC) have been published; however, outcomes remain ambiguous. MethodsPatients with synchronous oligometastatic stage IV NSCLC treated from 2005 to 2017 were enrolled to identify the impact of treatment sequence (primary lung resection vs systemic treatment) on progression-free survival (PFS) and overall survival (OS). ResultsTumor resection occurred in 51 patients (84% adenocarcinoma, 55% nonsmokers, and 65% driver gene mutation) before or after systemic treatment in 33 (64.7%) and 18 (35.3%) patients, respectively. Patients who received resection first were older (62.1 vs 54 years) and at a less advanced intrathoracic stage (18% vs 44%). No significant differences were noted regarding perioperative complications (30% vs 28%), hospital length of stay (9.0 vs 10.5 days), percentage of disease progression (91% vs 94%), overall death (70% vs 78%), median PFS (14.0 vs 22.8 months), and OS (44.6 vs 53.2 months). Patients with single-organ metastasis had significantly longer PFS and OS than those with oligometastases (17.5 vs 12.8 months, P = .040; and 55.6 vs 39.8 months, P = .035), respectively. Multivariable Cox analysis identified nonsolitary metastasis as the only independent predictor of PFS (hazard ratio, 2.27; 95% confidence interval, 1.07-4.81; P = .033). ConclusionsPrimary lung resection before or after induction systemic therapy may benefit patients with oligometastatic NSCLC. Future randomized clinical trials examining the effect of treatment sequence is recommended.

Site-Specific Metastasis and Survival in Papillary Thyroid Cancer: The Importance of Brain and Multi-Organ Disease.

Introduction-heterogeneity in clinical outcomes and survival was observed in patients with papillary thyroid cancer (PTC) and distant metastases. Here, we investigated the effect of distant metastases sites on survival in PTC patients. Methods-patients with a diagnosis of PTC and known metastases were identified using the Surveillance, Epidemiology, and End Results database (1975-2016). Univariate and multivariate Cox regression analyses were performed to analyze the effect of distant metastases sites on thyroid cancer-specific survival (TCSS) and overall survival (OS). Results-from 89,694 PTC patients, 1819 (2%) developed distant metastasis at the initial diagnosis, of whom 26.3% presented with the multiple-organ disease. The most common metastatic sites were lung (53.4%), followed by bone (28.1%), liver (8.3%), and brain (4.7%). In metastatic patients, thyroid cancer-specific death accounted for 73.2%. Kaplan-Meier curves showed decreased OS in patients with metastases to the brain (median OS = 5 months) and liver (median OS = 6 months) compared to lung (median OS = 10 months) and bone (median OS = 23 months). Moreover, multiple organ metastasis had a higher mortality rate (67.4%) compared to single organ metastasis (51.2%, p < 0.001). Using multivariate analysis, risk factors that significantly influence TCSS and OS were male gender (HR = 1.86, 95% CI = 1.17-2.94, p < 0.001, and HR = 1.90, 95% CI = 1.40-2.57, p = 0.009), higher tumor grade (HR = 7.31, 95% CI = 2.13-25.0, p < 0.001 and HR = 4.76, 95% CI = 3.93-5.76, p < 0.001), multiple organ involvement (HR = 6.52, 95% CI = 1.50-28.39, p = 0.026 and HR = 5.08, 95% CI = 1.21-21.30, p = 0.013), and brain metastasis (HR = 1.82, 95% CI = 1.15-2.89, p < 0.001 and HR = 4.21, 95% CI = 2.20-8.07, p = 0.010). Conclusion-the pattern of distant metastatic organ involvement was associated with variability in OS in PTC. Multi-organ metastasis and brain involvement are associated with lower survival rates in PTC. Knowledge of the patterns of distant metastasis is crucial to personalize the treatment and follow-up strategies.

Prognostic value of pretreatment F-18 fluorodeoxyglucose PET/CT in colorectal cancer with unresectable metastasis.

The aim of the study was to assess the prognostic value of pretreatment PET/computed tomography (CT) scans in colorectal cancer (CRC) patients with unresectable metastasis. We retrospectively reviewed the pretreatment PET/CT images of 82 CRC patients with unresectable metastasis and their medical records. On PET/CT images, maximum standardized uptake value (SUVmax) of primary tumor, highest SUVmax of metastatic tumors and number of metastatic organs were identified. The patients were further divided into single and multiple organ metastases groups according to the extent of disease. Survival analysis was performed with the clinical variables and metabolic parameters from PET/CT. In a total of 82 patients, the age of patients, highest SUVmax of metastatic tumors and number of metastatic organs were independent prognostic factors for overall survival (OS) (all P < 0.05), whereas the SUVmax of primary tumor was not. On multivariate analysis, only the SUVmax of metastatic tumor was a significant prognostic factor in the single organ metastasis group (P = 0.047), whereas the age and highest SUVmax of metastatic tumors were independent prognostic factors in the multiple organ metastases group (all P < 0.05). The highest SUVmax of metastatic tumors was an independent prognostic factor for OS in CRC patients with unresectable metastasis.

Ageing as key factor for distant metastasis patterns and prognosis in patients with extensive-stage Small Cell Lung Cancer.

Background: Small cell lung cancer (SCLC) represents about 13% of lung cancer cases, which is highly invasive and has a high mortality rate, with the 5-year overall survival (OS) rate being only 6.3%. Age at diagnosis of advanced SCLC is much older, but studies describing the ageing factor for distant metastasis patterns and prognosis of extensive-stage SCLC (ES-SCLC) are limited.Methods: Using the Surveillance, Epidemiology, and End Results (SEER) registry, we identified 18,682 patients with ES-SCLC (9,089 women and 9,053 men) who had complete clinical information between 2008 and 2015. Patients were classified into three groups (older group: ≥80 yrs, middle-aged group: 60-79 yrs, and younger group: ≤59 yrs). The role of different age at diagnosis of ES-SCLC (especially older group) in metastasis patterns was investigated, and OS and cancer-specific survival (CSS) of different age groups of metastatic ES-SCLC was assessed.Results: The most metastasis of ES-SCLC patients in the three groups was multiorgan metastases (MOM) metastasis (71.2%, 70.3% and 66.3%, respectively), the most single organ metastasis in the younger group was the lung (3.3%), the middle-aged group and the older group were the brain (3.5%, 3.1%, respectively). The analysis revealed that older patients were less likely to have MOM, but more likely to have all organs metastases than other two groups (p<0.001). Older group had the worst OS (p<0.001) and CSS (p<0.001). Furthermore, Radiotherapy and chemotherapy can improve survival (p<0.001), but the rate of radiotherapy and chemotherapy in older patients is lower than that in middle-aged and younger patients (50.4% vs 38.6% vs 20.7%, p<0.05). Compared with other two group, older group (odds ratios, ORs) for lung, all organ metastases, and MOM were 0.43 (95% CI 0.27-0.67), 1.77 (95% CI 1.55-2.03), 0.68 (95% CI 0.6-0.77), respectively.Conclusion: The mortality risk is highest with MOM and all organs metastasis followed by brain, lung, bone and liver metastases in elderly ES-SCLC patients. These results will be helpful for pre-treatment evaluation regarding the prognosis of ES-SCLC patients.

The contemporary role of metastasectomy in the management of metastatic RCC

Metastasectomy was initially described in the 1970s as a therapeutic strategy for patients with metastatic renal cell carcinoma. Since that time, systemic therapy options have grown exponentially, most recently with the introduction of immunotherapy. We aimed to review the contemporary literature regarding the role of metastasectomy in the era of targeted therapy and immunotherapy. Historically, metastasectomy has benefited patients with small volume, single-organ metastases, with favorable outcomes amongst younger, healthier patients with metastases to specific sites. The interplay between the employment of metastasectomy and systemic therapy has been limited to small, retrospective series with significant patient selection bias. More recently, investigators have conducted randomized controlled trials exploring the use of targeted therapies in the adjuvant setting after metastasectomy. Initial randomized data suggested no benefit in using sorafenib in this setting, and a subsequent study demonstrated possible harm in using pazopanib after metastasectomy. However, the role of other novel systemic therapies, including immunotherapy, nor the timing of use, have been meaningfully explored. Metastasectomy appears to be a valuable therapeutic option in the properly selected patient, requiring a multi-disciplinary management strategy and, pending future trials, a multimodal treatment approach.