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 Table of Contents  
ORIGINAL ARTICLE
Year : 2017  |  Volume : 50  |  Issue : 6  |  Page : 209-214

Multiple primary malignant neoplasms: Results from a 5-year retrospective analysis in a Metropolitan Hospital


1 Department of Colorectal Surgery, Jen-Ai Hospital, Taichung, Taiwan
2 School of Medical Informatics, Chung-Shan Medical University; Information Technology Office of Chung Shan Medical University Hospital, Taichung, Taiwan

Date of Submission21-Feb-2017
Date of Decision19-Apr-2017
Date of Acceptance17-Sep-2017
Date of Web Publication08-Dec-2017

Correspondence Address:
Dr. Chi-Chang Chang
School of Medical Informatics, Chung-Shan Medical University, Information Technology Office of Chung Shan Medical University Hospital, Taichung
Taiwan
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/fjs.fjs_28_17

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  Abstract 


Background: The high effectiveness of cancer screening and therapies resulted in the increased diagnosis of multiple primary malignancies (MPMNs) in Taiwan. The aim of the present study was to investigate the clinical data of patients and to determine the frequency and clinical features of MPMNs.
Methods: Between January 2010 and December 2014, a total of 2518 patients were screened and obtained retrospectively from the Tumor Registry Center of a metropolitan hospital. We quantified the clinical features and the most common cancer pairs of MPMNs using statistical and epidemiological indicators.
Results: Two hundred and eleven patients with MPMNs were evaluated. The median age at initial cancer diagnosis was 63 years old (range 12–100 years). The median age of diagnosis of secondary cancer was 67 years old (range 35–95 years). The median time between initial and secondary cancer diagnoses was 5 months (range 0–57.1). The overall incidence of MPMNs was 8.38%, and the male: female ratio was 2.01:1. The most frequent types of cancer at secondary diagnosis were digestive (79 patients, 3.05%), breast (22 patients, 0.87%), liver (22 patients, 0.87%), head-neck (18 patients, 0.71%), and bladder cancer (14 patients, 0.56%). In women, the most frequent types of cancer at secondary diagnosis were digestive (25 cases, 2.21%), breast (22 cases, 1.95%), liver (11 cases, 0.97%), lung (8 cases, 0.71%), and gynecologic cancer (7 cases, 0.62%). In men, the most frequent types of cancer at secondary diagnosis were digestive (54 cases, 3.89%), head-neck (16 cases, 1.15%), liver (11 cases, 0.79%), bladder (10 cases, 0.72%), and prostate cancer (10 cases, 0.72%). The most common cancer pairs in males were digestive/digestive (22 cases, 1.59%), head-neck/head-neck (4 cases, 0.29%), lung/digestive (3 cases, 0.22%), and prostate/bladder (3 cases, 0.22%). In addition, tobacco smoking, alcohol consumption, and betel-chewing were observed to be important risk factors for the development of MPMNs.
Conclusion: Indeed, the cancer registries can help us understand the disease better and use our resources to the best effect in prevention and treatment of MPMNs. In the present study, we discovered that patients with MPMNs tend to be older than those with a single primary malignant neoplasm. In conclusion, the clinical features and the most common cancer pairs of MPMNs are demonstrated in the present study. Based on these data, further analysis of the relationship between them is worthwhile.

Keywords: Multiple primary malignant neoplasms, retrospective analysis, tumor registry center


How to cite this article:
Sun CC, Chang CC. Multiple primary malignant neoplasms: Results from a 5-year retrospective analysis in a Metropolitan Hospital. Formos J Surg 2017;50:209-14

How to cite this URL:
Sun CC, Chang CC. Multiple primary malignant neoplasms: Results from a 5-year retrospective analysis in a Metropolitan Hospital. Formos J Surg [serial online] 2017 [cited 2020 Sep 23];50:209-14. Available from: http://www.e-fjs.org/text.asp?2017/50/6/209/220348




  Introduction Top


Over the past decades, the number of cases of cancer has been increasing worldwide. In Taiwan, among all cancer survivors, the 5-year survival rate is ~54% and the age-standardized mortality rates per 100,000 population increased steadily from 348.39 in 2002 to 401.18 in 2012. By 2020, an estimation of 99,491 new cases with cancer will be diagnosed.[1] However, the primary concern of cancer survivors is secondary cancer development and diagnosis. Previous studies indicated that the prevalence of multiple primary malignant neoplasms (MPMNs) ranged between 0.73% and 11.7%.[2],[3],[4] These numbers are primarily the result of early detection, supportive care, and advanced radiological and chemical treatments. The number of long-term cancer survivors has increased, as MPMNs are considered to be an important health issue. Nevertheless, the clinical correlation of MPMNs has not yet been clarified in Taiwan. The purpose of the present study was to evaluate the demographic and clinical features and the most common cancer pairs of MPMNs at the Tumor Registry Center of the Jen-Ai Hospital. To the best of our knowledge, this is the first study to study the clinical correlation of MPMNs.


  Methods Top


The present study was conducted at the Jen-Ai Hospital and approved by the Ethics Committee. The clinical datasets were obtained from the Tumor Registry Center of the hospital during a 5-year period between 2010 and 2014. Records without a distinct histopathological examination of each site and cases in which the second/third cancer was suspected to be a metastasis were excluded. According to the criteria of Taiwan Cancer Registry Sequence Number in Coding Manual, 2518 patients were included in the current study, of which 211 cases with more than one tumor site data were retrospectively evaluated. Demographic, pathological (site, date of diagnosis, histopathology and treatment), and clinical characteristics of patients were recorded in accordance with the international rules for multiple primary cancers (ICD-O-3). Statistical tests were performed for the analysis of demographic and clinical characteristics of patients, including a t-test for comparing the values in each group. P < 0.05 was considered statistically significant difference.

Ethical approval

The study was conducted in accordance with the Declaration of Helsinki and was approved by the local ethics committee of the institute. Informed written consent was obtained from all patients prior to their enrollment in this study.


  Results Top


Among the 2518 patients, 1387 (55.08%) were male and 1131 (44.92%) were female. Of 211 patients, 196 cases (7.78%) were diagnosed with cancer two times and 15 cases (0.6%) were diagnosed three times. The average diagnosis age of the single cancer was 62 years old (ranged from 12 to 100 years). The average diagnosis age of the first cancer was 63 years old (ranged from 12 to 100 years), and the average diagnosis age of the second cancer was 67 years old (ranged from 35 to 95 years). Both the first and second diagnosis of cancer demonstrated a significant statistical difference between the average age in the two gender groups (P = 0.008 for the first cancer and P = 0.006 for the second cancer). Average and minimum/maximum ages in subgroups were 31–40 years (31.44, 12/40), 41–50 years (46.03, 41/50), 51–60 years (55.58, 51/60), 61–70 years (65.51, 61/70), 71–80 years (75.56, 71/80), ≥81 years (84.87, 81/100). One hundred ninety-one patients were surpassing the 50-year-old age limit to diagnose the second and third cancer. The characteristics of the patients are presented in [Table 1].
Table 1: Patient characteristics in age groups

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The median period between the first and second cancer diagnosis was 5 months. Out of the total cases with two cancer diagnoses, 58 (38%) patients were diagnosed as synchronous and 15 (0.6%) as metachronous. From the patients diagnosed as synchronous, 48 cases (1.91%) were diagnosed within 1 month following the first cancer diagnosis and 10 cases (0.4%) were diagnosed 1–6 months after the first cancer diagnosis. From the patients diagnosed with metachronous, 2 (0.07%) cases were diagnosed 6–12 months after the first cancer diagnosis and 8 (0.32%) cases were diagnosed within 1 year after the first cancer diagnosis. The results indicate a strong positive correlation between the first and second cancer diagnosis and the patients' age (r = 0.86).

The five primary types of cancer observed during the first diagnosis were digestive cancer (694 patients, 27.56%), breast cancer (395 patients, 15.73%), liver cancer (355 patients, 14.10%), lung cancer (231 patients, 9.17%), and gynecologic cancer (166 patients, 6.59%). The five main types of cancer observed during the second diagnosis were digestive cancer (79 patients, 3.05%), breast cancer (22 patients, 0.87%), liver cancer (22 patients, 0.87%), head-neck cancer (18 patients, 0.71%), and bladder cancer (14 patients, 0.56%). In regard to the third diagnosis, the most frequently observed types were head-neck cancer (4 patients, 0.16%) and digestive cancer (4 patients, 0.16%).

[Table 2] depicts the locations of the first and second cancer diagnoses. The most frequent synchronous types of cancer observed were digestive (32 patients, 55.17%) and breast cancer (11 patients, 18.97%), whereas the most frequent metachronous types of cancer diagnosed were digestive cancer (4 patients, 26.67%) and bladder, cancer, breast, and lung cancer (2 patients, respectively, 13.33%). In addition, the most frequent histopathological cancer type encountered in the primary and second diagnoses was adenocarcinoma.
Table 2: Second primary cancers by site of first primary cancers

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[Table 2] presents the distribution of secondary types of cancer by site of the first primary cancer. Among all types of cancer, digestive cancer was constituted as the most frequent type: 28 (84.85%) cases were concurrent and 5 (15.15%) cases were subsequent. Breast cancer was constituted as the second most frequent type of cancer: 10 (90.90%) cases were concurrent and 1 (9.10%) case was leukemia. Similarly, gynecologic cancer was constituted as the third most frequent type of cancer, with 3 (100%) cases being concurrent. Finally, the last types of cancer observed were prostate cancer with only 1 (16.67%) case being concurrent, bladder cancer with 3 (50%) cases, and subsequent digestive and lung cancer.

The distribution of the men by site of the primary cancer was as follows [Table 3]: 462 cases of digestive cancer (33.31%), 250 cases of liver cancer (18.02%), 171 cases of prostate cancer (12.33%), 154 cases of lung cancer (11.10%), and 116 cases of head-neck cancer (8.36%). The most frequently diagnosed secondary types of cancer were digestive cancer (54 cases, 3.89%), head-neck cancer (16 cases, 1.15%), liver cancer (11 cases, 0.79%), bladder cancer (10 cases, 0.72%), and prostate cancer (10 cases, 0.72%). The most frequently diagnosed tertiary types of cancer were head-neck cancer (4 cases, 0.29%), digestive cancer (3 cases, 0.22%), liver cancer (2 cases, 0.14%), and bladder cancer (1 case, 0.07%)
Table 3: Most common cancer sites in patient population

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In women, the 3 most frequently diagnosed cancer pairs were breast/breast (10 cases, 0.88%), digestive/digestive (6 cases, 0.53%), and gynecologic/gynecologic (3 cases, 0.27%). The 4 most frequently diagnosed cancer pairs in men were digestive/digestive (22 cases, 1.59%), head-neck/head-neck (4 cases, 0.29%), lung/digestive (3 cases, 0.22%), and prostate/bladder (3 cases, 0.22%) [Table 4].
Table 4: Most common cancer pairs according to both genders

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From the above cases, 465 (18.47%) cases were smokers (the average was 65; ranged from 24 to 94). With regard to the habit of drinking alcohol, 366 (14.54%) patients were alcohol consumers. One hundred fifty-seven (6.08%) patients were betel chewers and the body mass index (BMI) of patients during the first diagnosis was 24 (range 13.0–41.0). There were 1496 patients evaluated for recurrence or metastasis disease from digestive cancer (388 patients, 25.94%), from the liver cancer (317 patients, 21.19%), from lung cancer (235 patients, 15.71%), breast cancer (161 patients, 10.76%) and prostate cancer (123 patients, 8.22%).


  Discussion Top


According to the literature, cancer survivors have an increased risk of developing MPMNs. The present study demonstrated a significantly increased risk of developing MPMNs whose sites depend on the primary cancer. A previous study indicated that the prevalence of MPMNs ranged from 0.73% to 11.7%.[2],[3],[4] Other studies stated that the MPMNs ratio of male to female ranged from 0.9:1 to 3.5:1.[5],[6],[7],[8] In the present study, the overall incidence of MPMNs was 8.38%, and the male: female ratio was 2.01:1. Furthermore, compared to the metachronous survivors, the synchronous group of survivors demonstrated a higher incidence (20.55% and 79.45%, respectively). In contrast to our results, a previous study on 72 Chinese patients by Jiao et al. reported that 22.2% of MPMNs were diagnosed as synchronous and 76.4% as metachronous.[8] Finally, no significant difference among the age of the MPMNs diagnosis was observed.

The mechanisms of MPMNs have not yet been well defined. There are multiple factors that may cause MPMNs, such as genetic susceptibility, environmental factors, radiotherapy and chemotherapeutic agents used in the treatment of cancer, and certain types of cancer share common risk factors. Previous studies stated that continuous smoking and the alcohol consumption increase the risk of MPMNs.[9],[10] In the present study, the percentage of male smokers is 17.59% and 0.87% for female smokers. In patients with MPMNs, continuous smoking appeared to associate with digestive, head-neck, lung, liver, bladder, and prostate cancer.[11],[12] These findings were consistent with previous studies.[3],[13] The present study identified that cancer survivors with a continuous smoking habit had significantly increased risks of developing MPMNs and these results were consistent across all age groups. In addition, it is argued that the habit of drinking alcohol may be an important factor for the development of MPMNs.[3] In our patient group, 330 (13.11%) male and 36 (1.43%) female patients were consuming alcohol. The habit of drinking alcohol was correlated with MPMNs of the digestive, head-neck, and lung cancer. Similarly, previous studies implicated that the habit of drinking alcohol is associated with numerous types of MPMNs.[3],[13],[14] Furthermore, betel-nut chewing is a risk factor of pharyngeal cancer and for the development of MPMNs. With regard to betel-nut chewing, 4 (0.16%) female and 153 (6.08%) male patients were identified. For patients with MPMNs, betel-nut chewing was associated with head-neck, digestive, liver, lung, and bladder cancer. Similar findings were reported by Auluck et al.[15] and Franke et al.[16] Dietary factors also play a role in carcinogenesis and are considered to be a moderate risk factor for digestive cancer.[17] It is a known fact that certain MPMNs share etiological risk factors. We have observed a higher risk of MPMNs in our data. In addition, the increased overall risk for patients with MPMNs was also statistically significant. Several theories were suggested for this increased incidence, such as environmental factors playing a role in the development of MPMNs.[18] Based on the “field cancerization” theory, the carcinogenic effects of tobacco and alcohol lead toward the development of MPMNs.[3] Nonetheless, cancer survivors should be educated and encouraged to modify their lifestyle (the cessation of smoking, alcohol, betel-nut chewing, lack of exercise, and unhealthy diet).

In the present study, the most frequently diagnosed cancer pair of MPMNs was breast/breast in female patients. A previous study indicated that cancer survivors with breast cancer are at a high risk of developing gynecologic and digestive cancer, in agreement with our results.[19] In the male patients group of the present study, the most frequently diagnosed cancer pair was digestive/digestive. The risk factors that may be associated with this result are smoking and a synergetic effect of drinking and dietary factors. The data of the current study demonstrated that primary digestive cancer increases the risk of developing MPMNs, particularly colon and gastric cancer.

There have been numerous reports addressing the different cancer sites which are likely to be associated with treatment modalities for developing MPMNs. Unfortunately, it is not easy to trace the treatment modalities and recurrence for our patients, as the collected data were not enough for further analysis. In addition, previous studies argued that genetic, hereditary, and nutritional factors and the immune system of patients may be important risk factors for the development of MPMNs.[20],[21]


  Conclusion Top


Due to early detection, effective therapies, and appropriate intervention, the probability of appearance of MPMNs in the same patient has increased. As a prioritized Act of National Cancer Control and Prevention 4 year Plan in 2005, the Taiwan government has focused on lowering the rate of incidence and mortality. While the risk of MPMNs has been extensively studied, very few papers have included the Taiwan population. Indeed, the cancer registries can help us understand the disease better and use our resources to the best effect in prevention and treatment of MPMNs. Hospital-based tumor registries provide the advantage of cancer survivors' information; however, the related therapy data are quite limited, such as incomplete long-term treatment sequelae. The cases of cancer survivors in Taiwan will increase exponentially over the next decade. We discovered that patients with MPMNs tend to be older than those with a single primary malignant neoplasm. In addition, there is an elevated risk for cancer survivors to develop MPMNs, such as body fat distribution may influence the association between obesity and several cancers. In conclusion, we are presenting the clinical features and the most common cancer pairs of MPMNs to further analyze the risk factors described in the present study.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Wu M, Zhao JK, Zhang ZF, Han RQ, Yang J, Zhou JY, et al. Smoking and alcohol drinking increased the risk of esophageal cancer among Chinese men but not women in a high-risk population. Cancer Causes Control 2011;22:649-57.  Back to cited text no. 14
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Auluck A, Hislop G, Poh C, Zhang L, Rosin MP. Areca nut and betel quid chewing among South Asian immigrants to Western countries and its implications for oral cancer screening. Rural Remote Health 2009;9:1118.  Back to cited text no. 15
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