Clinical characteristics and prognostic factors in elderly patients with metastatic pancreatic cancer: a population-based study

Background: The aim of this study was to evaluate the prognostic factors of elderly patients with metastatic pancreatic cancer (mPC). Methods: Patients diagnosed with mPC between2004 and2014 were identified from the Surveillance Epidemiology and End Results (SEER) database. Clinical characteristics and prognostic factors in elderly patients with mPC were examined. Results: A total of 10784 mPC patients between 65 and 80 years old were included and divided into three age groups. Elderly mPC patients differed from younger patients in many aspects, including marital status, race, gender, T stage, N stage, treatment regimen, prognosis, cause of death, and metastatic characteristics (p<0.001). An analysis of the prognostic factors showed that chemotherapy, as the main treatment for the elderly, can significantly improve their prognosis, while surgery can improve the prognosis of patients between 65 and 80 years old. Other factors, including gender, marital status, T stage, and site of metastasis, had different effects on patients in different age groups. Conclusion: Elderly patients with mPC are a special group of individuals whose clinical characteristics and prognostic factors are different from those of younger patients and require special treatment and attention.

Clinical characteristics and prognostic factors in elderly patients with metastatic pancreatic cancer: a population-based study CURRENT  Henan provincial people's hospital the fourth leading cause of tumor-related death and is expected to become the second leading cause by 2030 in the US [4,5]. Its poor prognosis is due to difficulties in early diagnosis; therefore, most patients are diagnosed at an advanced stage accompanied by metastasis (stage IV) [3].
The association between aging and cancer has been widely recognized, as the elderly's internal environment (chronic inflammation and immune system dysfunction) is more likely to induce cancer under the stimulation of carcinogens [6,7]. Moreover, the immune system plays a key role in the development of pancreatic cancer [8]. Therefore, elderly patients represent a distinct subgroup, and more targeted clinical management plans are needed for these patients. At present, surgery is not recommended for pancreatic cancer patients with distant metastases, especially the elderly, which are more likely to receive chemotherapy, radiotherapy and other nonsurgical treatments [3,9].
Due to the aging population, it is not difficult to predict that the number of elderly patients with metastatic pancreatic cancer (mPC) will increase further. However, the clinical management of this group of patients is still lacks effective attention; therefore, the aim of this study was to explore the clinical characteristics and prognostic factors in elderly patients with mPC.

Patient cohort
The data examined in the present study were retrieved from the SEER-18 registry of the

Patient characteristics
The clinical characteristics of the mPC patients stratified by age are presented in Table 1 On the other hand, there was a large proportion of mPC patients older than 80 years who were unmarried (which is adverse to mPC patients between the ages of 65 and 80 years), White, female, withT1 and T2 stage, and with N0 stage disease (all P <0.001)and were less likely to be treated with surgery, radiation and chemotherapy. Moreover, the elderly may face more difficulties when identifying metastatic sites, which include the liver, lung, brain and bone (all of these sites have a lower diagnosis rate in elderly patients than in younger patients; all P <0.001, Table 1).
The analysis also indicated that elderly mPC patients had a higher mortality rate at the follow-up deadline but a lower tumor-specific mortality rate than younger patients(all P

Prognostic factors of mPC patients between 65 and 80 years old.
Multivariate Cox regression analysis revealed that surgical resection was associated with improved (HR = 0.70, 95% CI = 0.57-0.85) and CSS (HR = 0.72, 95% CI = 0.58-0.90), and chemotherapy was also related to improved (HR = 0.45, 95% CI = 0.41-0.49) and CSS (HR = 0.43, 95% CI = 0.39-0.48) ( Table 2). The correlation of chemotherapy to OS and CCS with the log-rank test was also revealed in the survival curve ( Figure 1).Moreover, the results demonstrated that factors associated with poor OS included being unmarried, T0 stage and lung metastasis. In addition, poor CSS was inclined to occur in patients with the following characteristics: T0 stage and lung metastasis. The detailed patient characteristics are shown in Table 2.
Prognostic factors of mPC patientsover80 years old.
Multivariate Cox regression analysis indicated that chemotherapy was associated with  Table 3). The relation of chemotherapy and surgical resection to OS and CCS with the logrank test was also revealed in the survival curve ( Figure 2). Moreover, the analysis indicated that factors associated with poor OS included male gender and liver metastasis (Table 3).

Discussion
According to the characteristics of the age group reported previously [3], the elderly patients in this study were divided into the 65-to 80-year-old group and the over80-yearoldgroup. The statistical results showed that the elderly accounted for the majority of all mPC patients (65.9%), especially those between 65 and80 years old (40.9%).A comparison of the clinical characteristics of patients of different ages revealed that old age and White race, which may be related to a longer life span, as most Whites hold a higher level of living standards and have more access to medical services) were favorable prognostic factors.
The results also showed that old age and female sex were favorable prognostic factors for mPC patients over 80 years old. Both of these factors can be explained: females pay more attention to their health and have a better lifestyle than males and therefore live longer than males regardless of the development of mPC. In addition, the marriage rate of patients between 65 and 80 years old was the highest (54.3%), while the marriage rate of patients between 65and 80 years old declined sharply (37.1%), which may be related to the higher death rate of their marriage partner at their age. Further prognostic analysis also indicated that marriage is a favorable prognostic factor for mPC patients between 65 and80 years old, which agrees with many previous studies [10][11][12][13].Therefore, elderly patients who do not have family members should be given more attention.
Interestingly, although the stage of many patients is unknown, there was an increase in the proportion of patients with T1 and T2 stage disease and a decrease in the proportion of patients with lymph node negative stage (N0) disease in elderly patients ranging in age between65 and80 years and above compared to younger patients. As the TNM stages of many patients are unknown, we cannot provide a reasonable explanation, which needs further research to confirm. Surprisingly, prognostic factor analysis suggested that patients with T0 stage disease between 65 and80 years oldhad a better prognosis than those with Tn stage disease. This may be because pancreatic cancer has metastasized at an earlier T stage, indicating that the tumor has a stronger ability to invade and metastasize; therefore, the tumor is more malignant, and the prognosis is correspondingly worse. This result is consistent with those froma previous study [12].
Generally, the older the patient is, the worse his/her health tends to be, and the more serious the basic diseases, the more likely he/she is to die from the basic disease [3,9], which was confirmed by our results. The present study showed that the overall mortality rate was higher in older patients; however, the tumor-specific mortality rate decreased Similarly, thepresent analysis also indicated that lung metastasis, which is related to both OS and CCS, isa poor prognostic factor for patients between 65 and80 years old, while liver metastasis is related to OS in those over 80 years old.
Data on treatment showed that the older the patient is, the less likely he or she is to receive treatment, including surgery, radiation and chemotherapy.By contrast, chemotherapy is the most common form of treatment, followed by surgery, and radiation is minimal. Further analysis suggested that the greatest therapeutic benefit for patients between 65 and80 years old and older is chemotherapy. Chemotherapy has been proven to be the primary treatment for mPC [14][ [15][16][17] . Gemcitabine alone or in combination with other chemotherapeutic drugs and the FOLFIRINOX regimen (leucovorin, fluorouracil, irinotecan, and oxaliplatin) are recommended according to the performance status as well as the comorbidity profile of the patient [18] . Surgical treatment is not suggested for mPC, especially for elderly patients, according to clinical guidelines. However, it was demonstrated to improve the prognosis of mPC patients [12]. The present analysis also indicated that patients between 65 and80 years old may still benefit from surgery but not those over 80 years old, which may be because they are too old and in poor health to tolerate surgery. Metastatic cancers originating from renal cells [19] , the colorectum [20] , and prostate [21,22] have been proven to benefit from local treatment of the primary tumor. Two recent large-scale population-based studies demonstrated that survival can be prolonged through local treatment for metastatic prostate cancer [22,23] . All the above information suggests the clinical value of surgical treatment in the management of mPC.
Although radiotherapy has a positive effect on OS among those between65 and80years old, it fails to show a correlation with CCS, which also shows no association with death in patients over 80 years old. Possible reasonsfor this finding may be that pancreatic cancer is less sensitive to radiotherapy or the intolerance to radiotherapy in the elderly [15,24].
The present study utilized a population-based cohort, which has the advantage of

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Competing interests
The authors declare that they have no competing interests.