Prognosis and survival analysis of patients with pancreatic cancer: retrospective experience of a single institution

Background The overall survival of patients with pancreatic cancer is extremely low. Despite multiple large-scale studies, identification of predictors of patient survival remains challenging. This study aimed to investigate the prognostic factors for pancreatic cancer. Methods The clinical data of 625 patients with pancreatic cancer treated at Shengjing Hospital of China Medical University from January 2013 to December 2017 were collected. Results Of 625 patients, 569 were followed from 1 to 75 months. The median overall survival was 9.3 months. The overall 1-, 3-, and 5-year survival rates were 37.8%, 15.1%, and 10.5%, respectively. Cox proportional hazards model indicated that baseline carbohydrate antigen 199 level, neutrophil-lymphocyte ratio, operative procedure, lymph node metastasis, number of distant organ metastasis, and postoperative adjuvant chemotherapy were independent prognostic factors of patients with pancreatic cancer. Baseline carbohydrate antigen 199 level, degree of weight loss, operative procedure, lymph node metastasis, number of distant organ metastasis, and postoperative adjuvant chemotherapy were independent prognostic factors of pancreatic head cancer subgroup. Baseline carbohydrate antigen 199 level, carcinoembryonic antigen level, total bilirubin level, neutrophil-lymphocyte ratio, peripancreatic invasion, number of distant organ metastasis, and postoperative adjuvant chemotherapy were independent prognostic factors of the pancreatic body/tail cancer subgroup. Conclusions Higher carbohydrate antigen 199 levels, neutrophil-lymphocyte ratio, lymph node metastasis and distant organ metastasis predict a poor prognosis in patients with pancreatic cancer. Early detection, early radical surgery and adjuvant chemotherapy are needed to improve prognosis for this deadly disease.

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.

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 < 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.

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&lt;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 &lt; 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 &gt; 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 &gt; 6cm, and multi-organ metastasis were independent influencing factors for poor overall survival and cancer-specific survival prognosis in patients with metastatic hepatocellular carcinoma.

Cancer of unknown primary stem-like cells model multi-organ metastasis and unveil liability to MEK inhibition

Cancers of unknown primary (CUPs), featuring metastatic dissemination in the absence of a primary tumor, are a biological enigma and a fatal disease. We propose that CUPs are a distinct, yet unrecognized, pathological entity originating from stem-like cells endowed with peculiar and shared properties. These cells can be isolated in vitro (agnospheres) and propagated in vivo by serial transplantation, displaying high tumorigenicity. After subcutaneous engraftment, agnospheres recapitulate the CUP phenotype, by spontaneously and quickly disseminating, and forming widespread established metastases. Regardless of different genetic backgrounds, agnospheres invariably display cell-autonomous proliferation and self-renewal, mostly relying on unrestrained activation of the MAP kinase/MYC axis, which confers sensitivity to MEK inhibitors in vitro and in vivo. Such sensitivity is associated with a transcriptomic signature predicting that more than 70% of CUP patients could be eligible to MEK inhibition. These data shed light on CUP biology and unveil an opportunity for therapeutic intervention.

A Possible Definition of Oligometastases in Pancreatic Cancers and Their Survival Outcomes

Background: Among advanced metastatic cancers, oligometastatic cancers (OM) are defined as having limited visible metastases, possibly associated with relatively better survival outcomes. We attempted to identify cases that are in line with the concept of OM among unresectable metastatic pancreatic cancer, using a retrospective cohort.Methods: A total of 130 cases with unresectable metastatic pancreatic cancer received non-curative surgery (palliative surgery or staging laparotomy) from April 2001 to December 2019. Metastatic sites, clinicopathological information, and surgical outcomes were collected to reveal definition of OM.Results: Primary tumor sites were pancreatic head in 80 cases and others in 50 cases. Performed operations were gastrointestinal tract bypass in 68 cases and staging laparotomy in 62 cases. Based on the survival outcome differences, OM criteria were defined as single organ metastasis, a few countable lesions (4 or fewer organ metastases or limited peritoneal metastases) and low serum CA19-9 level (< 2000 U/ml). The median overall survival time (MST) after non-curative surgery of OM cases (n=54) was 13.0 months and was significantly better than non-OM cases (n=76) (MST:8.4months, P = 0.003).Conclusion: 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 CA19-9 (< 2000 U/ml) as a new criteria for OM.

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.

Prognosis classification of breast cancer with distant lymph node metastasis IIIc or M1 category

Background: In the American Joint Commission on Cancer (AJCC) staging manual, ipsilateral supraclavicular lymph node metastases (ISLM) were defined as N3c, while contralateral supraclavicular and subclavian lymph node, contralateral internal mammary lymph node, contralateral axillary lymph node, and cervical lymph node as distant lymph nodes metastasis (DLM) were classified as M1, stage IV. Herein, we used the information recorded in the Surveillance, Epidemiology, and End Results (SEER) database to compare patients' overall survival with DLM, ISLM, and distant organ metastasis. Methods: A total of 376 patients with ISLM, 562 patients with DLM, 5,069 patients with IIIc stage breast cancer, and 7,540 patients with distant organ metastasis from the SEER database (2004-2016) were included in the present study. R package was used to perform the Kaplan–Meier survival analysis among these four groups, and propensity score weighting (PSW) was used to minimize the differences in clinicopathological characteristics among groupsResults: After PSW, the median survival of ISLM, DLM, IIIc stage, and distant organ metastasis was 42 months, 50 months, 55 months, and 31months, respectively. DLM achieved significantly better overall survival than distant organ metastasis (p<0.001, HR=0.646, 95%CI:0.561-0.737), while there was no significant difference in long-term survival between DLM and ISLM (p=0.467, HR=0.915, 95%CI:0.719-1.163) or DLM and IIIc stage (p=0.959, HR=0.995, 95%CI:0.837-1.183). Surgery (p<0.001, HR=0.502, 95%CI:0.375-0.674) and chemotherapy (p=0.007, HR=0.701, 95%CI:0.527-0.932) could significantly improve the OS for patients with DLM. When compared with chemotherapy alone, a combination of chemotherapy, surgery, and radiotherapy could achieve better survival, with the increased median survival from 26 months to 82 months (p<0.001, HR=0.366, 95%CI:0.253-0.529).Conclusion: The prognosis of breast cancer patients with DLM was similar to ISLM and IIIc stage, but much better than that of patients with distant organ metastasis. Also, combined-modality therapy significantly improved long-term survival. Consequently, it seems more reasonable to classify DLM as IIIc category instead of M1.