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Clinical features of the patient with multiple primary tumors: Single center experience

Clinical features of the patient with multiple primary tumors: Single center experience Orıgınal Article MEDICAL ONCOLOGY North Clin Istanb 2017;4(1):43–51 doi: 10.14744/nci.2017.67044 Clinical features of the patient with multiple primary tumors: Single center experience 1 2 2 2 2 Ali Gokyer, Osman Kostek, Muhammet Bekir Hacioglu, Bulent Erdogan, Hilmi Kodaz, 2 2 2 2 Esma Turkmen, Ilhan Hacibekiroglu, Sernaz Uzunoglu, Irfan Cicin Department of Internal Medicine, Trakya University Faculty of Medicine, Edirne, Turkey Division of Medical Oncology, Department of Internal Medicine, Trakya University, Balkan Oncology Hospital, Edirne, Turkey ABSTRACT OBJECTIVE: Multiple primary tumors are the ones that develop in the same patient at the same or different times. They are usually examined under two groups. If the second tumor is diagnosed 6 months after the first tumor is diagnosed, it is named as metachronous tumor. If it is diagnosed in 6 months after the first diagnosis, it is called as synchronous tumor. The malignancy of tumors should be proved histologically. At least 2 cm of solid tissue should be present between two tumors. If they are at localized at the same place, a gap of at least 5 years should be present between them. Metastatic disease should be eliminated.This study aimedto review the clinical, demographic, and pathological features of multiple primary tumors, detect the prevalence, compare the results with literature findings, and evaluate and improve the approach to multiple primary tumors. METHODS: A total of 170 patients diagnosed with multiple primary tumors were included in this study. Patient data were obtained from pathology and medical reports of the patients. RESULTS: Most of the multiple primary tumors were metachronous. The number of male patients was more than that of female patients. The median time between double tumors was 3 monthsforsynchronous tumorsand 26 months for metachronous tumors. Synchronous tumors with the highest prevalence of comorbidity were lung–lar- ynx and lung–colon, whereas metachronous tumors with the highest prevalence of comorbidity were lung–blad- der, lung–larynx, breast–endometrium, and breast–colon. The history of smoking and alcohol was found to be higher in male patients andsynchronous tumors. CONCLUSION: The detection of the first tumor in the metastatic stage and an accompanying synchronous sec - ondary tumor was found to be a poor prognostic factor. The treatment of the first tumor, smoking, squamous cell histology, and male gender were among the other factors negatively affecting survival,although they were not statistically significant. Keywords: Metachronous; multiple primary tumors; survival; synchronous. ultiple primary tumors are the ones that dier ff ent times,accounting for 0.7%–11% of all car - Mdevelop in the same patient at the same or cinomas [1, 2]. If the second tumor is diagnosed Received: January 09, 2017 Accepted: April 05, 2017 Online: May 10, 2017 Correspondence: Dr. Osman KOSTEK. Trakya Universitesi, Ic Hastaliklari Anabilim Dali, Tıbbi Onkoloji Bilim Dali, Balkan Onkoloji Hastanesi, Edirne, Turkey. Tel: +90 284 - 235 76 41-1851 e-mail: [email protected] © Copyright 2017 by Istanbul Northern Anatolian Association of Public Hospitals–Available online at www.kuzeyklinikleri.com 44 North Clin Istanb 6 months after the first tumor is diagnosed, it is A total of 10.000 files related to patients with cancer named as metachronous tumor, whereas if it is di- diagnosis were evaluated agnosed in 6 months after the first diagnosis, it is called as synchronous tumor [3]. The formation 190 patients with of the second tumor occurs as a result of a series multiple primary tumor of complex interactions. The first tumor increases the risk of developing secondary tumor [4]. Also, 10 patients smoking, alcohol intake, environmental factors, and with BCC were excluded genetic mutations increase the risk of developing secondary tumor. The chances of developing sec- 180 subjects were ondary tumorsare increased by additive and syner- included to the study gistic ee ff ct of the treatment with combined chemo - therapy and radiotherapy applications. All patients 49 patients with 121 patients with should undergo special surveillance and should be Synchronous tumor Metachronous tumor followedup and treated with methods such as pro- phylactic surgery if necessary. Figure 1. Method of selection of patient group. This studyaimed to evaluate the clinical, de - mographic, and pathological features of multiple coexistence of double tumors and their fates, diag- primary tumors,and compare the results with lit- nosis date of the tumors, and dier ff ence between erature findings. The findings might contribute to their diagnosis dates in months was recorded. Tu- future approaches to multiple primary tumors. mor stage was considered as metastatic disease and organ-limited disease. The smoking history of the MATERIALS AND METHODS patient was identiefi d as having a cigarette story or not smoking. The tissue diagnoses in pathol- Patient features ogy reports were noted. Tumor treatment options This was a retrospective descriptive case series were obtained from follow-up and treatment files. study, and all the cases with cancer diagnosis in the Treatment options were also categorized as cura- Trakya University medical oncology department tive and noncurative. If the secondtumor is diag- between 2005 and 2015 were evaluated retrospec- nosed 6 months after the first tumor is diagnosed, tively. The medical recordsof 10,000 patients were it is named as metachronous tumor, whereas if it is analyzed before the study. The medical records of diagnosed in 6 months after the first diagnosis, it 180 patients with multiple primary tumors were in- is called as synchronous tumor. Also, each tumor cluded in the study. The patients with basal cell skin with tissue biopsies was shown to be malignant carcinoma as one of the tumors,out of 10 patients with clinical and histological features, indicating with multiple primary tumors, were excluded from that these tumors did not occur due to recurrence the study (Figure 1). or metastasis of other tumors. The cases without tissue diagnosis or the ones with tissue diagno- Study design sis whose tumor could not be shown as malignant The age and sex of the patients, history of smoking with immunohistological and/or histopathological and alcohol use, age of first tumor diagnosis, first staining were not included in this study. The fate of tumor organ, first tumor histology, first tumor site, the patients was given as dead or being followedup. first tumor stage, first tumor treatment, second tu - The present age of the patients who were being fol- mor age, second tumor organ, second tumor histol- lowedup was determined. The age on the death date ogy, second tumor site, second tumor stage, second and the death date were also determined for the tumor treatment, synchronous and metachronous dead patients. Based on the pathology reports, the Gokyer et al., Clinical features of the patient with multiple primary tumors exact diagnosis dates of the first and second tumors colon (10), lung (9), larynx (6), prostate (4), skin (4), were recorded. The time between these two dates breast (3), bladder (3), endometrium (3), pancreas was recorded in months.Medical oncology records, (2), stomach (2), thyroid (1), ovary (1), esophagus hospital files, automation system, and pathology (1). Thirty-three (67.3%) of these tumors had ad- laboratory records were used during data collection. enocarcinoma histology, 14 (28.6%) had squamous The information on the recent status of the patients cell carcinoma histology, 1had follicular carcinoma, who had at least 6 months over their last follow- and 1had melanoma histology. Twenty-one patients up was provided by phone. The death records were (42.9%) had metastatic disease, and 28 patients obtained from the Ministry of Health death noti- (57.1%) had organ-limited disease. c fi ation system. The date of diagnosis was taken as The prevalence order of the origin of second- the time of the pathologic diagnosis or the time of ary tumorin the patients with synchronous tumor surgery in patients without preoperative diagnosis. waslungs (15), colon (10), kidney (5), bladder (4), prostate (3), ovary(3), larynx (3), pancreas (2), en- Statistical analysis dometrium (1), and stomach (1). Thirty-eight of these tumors (76.6%) had adenocarcinoma histol- Univariate and multivariate analyses were per- ogy, and 11 tumors (22.4%) had squamous cell car- formed. Mean and median values of the patients cinoma histology. Twenty-two patients (44.9%) had were determined by descriptive statistics. Standard metastatic disease, whereas27 patients (55.1%) had deviation (±) was used. The parametric variables organ-limited disease. were compared between groups using theindepen- dent-samplet test. Nonparametric variables were Twenty-nine (59.2%) of the patients with syn- evaluated using the chi-square test. Kaplan–Meier chronous tumor died, and 20 patients (40.8%) car- method was used for survival analyses. The confi- ried on with their clinical follow-ups. When the dence interval was considered as 95%, and a p value co-occurrence of double tumors was analyzed in less than 0.05 was considered as statisticallysignifi- months, the mean was 2.63±1.56 (median 3; range cant. All data were entered in SPSS 20.0 for Win- 0–6). Co-occurrence was most frequently detected dows (SPSS; Chicago, IL, USA). in five patients with colon–lung and fivepatients with lung–laryngeal (Table 2). RESULTS One hundred and twenty-one patients with metachronous tumors were detected. Forty- Study group features nine of these patients were female (40.5%) and The prevalence of multiple primary tumors was 72male (59.5%). The mean age of the patients was 1.9% in all patients. The patients were basically di- 62±12.13 years (median 63 years; range 36–89 vided into two groups: ones with synchronous and years). Thirty patients (24.8%)drank alcohol, and metachronous tumors. Further, 49 patients (28%) 91 patients (75.2%) did not drink alcohol. Of the hadsynchronous tumors and 121 patients (72%) patients, 61 (50.4%) had smoking history and 60 hadmetachronous tumors (Figure 1). (49.6%) of them did notsmoke. The clinical and demographic data of the pa - The mean age of primary tumor in patients with tients areshown in Table 1. The rate of smoking was metachronous tumors was 56±13.00 (median 57, signicfi antly higher in patients with synchronous range 20–88). According to the prevalence order tumorsthan in patients with metachronous tumors. of the tumor source, tumorswere detected in the Similarly, the rates of metastatic disease were high- breast (25), colon (16), larynx (16), bladder (12), erin patients with synchronous tumors than in pa- prostate (9), skin (8), endometrium (8), lungs (7), tients with metachronous tumors (Table 1). kidney (6), ovary (5), testis (2), stomach (2), thyroid The prevalence order of the origin of primary (1), nose (1), esophagus (1), liver (1), and cervix (1). tumor in the patients with synchronous tumorswas Of these tumors, 89 had adenocarcinoma histology 46 North Clin Istanb Table 1. Clinical and demographic characteristics of subjects Synchronous tumour Metachronous tumour (n=49) (n=121) n % n % Age, year 64±12 62±12 Gender, M/F 11/38 49/72 Smoking* 33 67.3 61 50.4 Alcoholconsumption 13 26.5 30 24.8 Histopathology of primarytumour, Adenocancer 33 67.3 89 73.5 Squamouscellcancer 14 28.6 29 24.0 Others** 2 4.1 3 2.5 Stage of primarytumour** Localized 28 57.1 97 80.2 Metastatic 21 42.9 24 19.8 Histopathology of secondarytumour Adenocancer 38 76.6 94 77.6 Squamouscellcancer 11 22.4 26 21.4 Stage of secondarytumour Localized 27 55.1 69 57.1 Metastatic 21 44.9 52 42.9 Time intervalbetweensecondtumour (month)** Median (Interquartile range) 3 (1–4) 26 (13–68) Minimum- maximum 0–6 7–312 Clinicaloutcome Death 29 59.2 61 50.4 *p<0.05; **Insynchronous tumours, 1 patient had tyroid follicular cancer and the other patient had malign melanoma. In metachronous group, 2 patients had pure seminoma, theother had thyroid follicular cancer. (73%), 29 had squamous cell carcinoma histology carcinoma histology (77.7%), 26 had squamous cell (24%), 2 had seminoma histology (1.7%) and 1 had carcinoma histology (21.5%), and 1 had follicular follicular cancer histology. Twenty-four patients cancer histology. Sixty-nine patients (57%) had (19.8%) had metastatic disease, whereas 97 patients metastatic disease, and 52 patients (43%) had an (80.2%) had an organ-limited disease. organ-limited disease. The mean age of the secondary tumor in pa - Of patients with a metachronous disease, 61 tients with metachronous tumors was 60±12.8 patients (50.4%) died and 60 patients (49.6%) years (median 61; range 34–89). The tumors were continued with their treatment in the outpatient classie fi d according to the prevalence orderas lung clinic.The mean age of the co-occurrence of double (35), colon (21), breast (9), bladder (8), endome- tumors in months was 50±60.26 months (median trium (8), prostate (7), kidney (6), larynx (6), pan- 26months; range 7–312 months). In terms of tu- creas (3), skin (3), stomach (2), tongue (2), thyroid mor co-occurrence, 10 patients with lung–blad- (2), esophagus (1), biliary tract (1), and ureter (1) der, 10 patients with larynx–lung, 9 patients with (Table 2). Ninety-four of these tumors had adeno- breast–endometrium, 8 patients with breast–co- Gokyer et al., Clinical features of the patient with multiple primary tumors Table 2. Tumours location in patients with multiple primary tumours related to their organ involvement Synchronous Metachronous Synchronous Metachronous tumour (n=49) tumour (n=49) tumour (n=49) tumour (n=49) Colon, n (count) Larynx – 1 Lung 5 4 Stomach, n (count) Kidney 3 1 Pancreas 1 – Endometrium 3 2 Prostat 1 – Colon 2 – Endometrium – 1 Prostat 2 – Tongue – 1 Bladder 1 3 Kidney, n (count) Skin 1 1 Thyroid 1 – Larynx 1 – Lung – 3 Ovary – 2 Colon – 1 Stomach – 1 Skin – 1 Lung, n (count) Bladder – 1 Larynx 5 – Breast, n (count) Pancreas 3 – Colon – 7 Skin 3 – Endometrium – 5 Bladder 2 4 Ovary – 4 Kidney 1 2 Breast – 3 Stomach 1 – Kidney – 2 Breast 1 – Thyroid – 2 Prostat 1 1 Lung – 2 Ovary 1 – Endometrium, n (count) Larynx, n (count) Breast – 4 Lung – 9 Lung – 3 Prostat 1 3 Colon – 2 Skin 1 1 Prostat, n (count) Bladder 1 – Colon – 6 Pancreas – 2 Larynx – 2 Tongue – 1 Lung – 1 Bladder, n (count) Skin, n (count) Lung – 6 Lung – 5 Prostat 2 2 Breast – 1 Skin 1 – Colon – 1 Larynx – 2 Esophagus, n (count) Colon – 2 Lung – 1 Ovary, n (count) Thyroid, n (count) Breast 2 1 Kidney – 1 Endometrium 1 – Testis, n (count) Colon – 2 Lung – 1 Pancreas – 1 Ureter – 1 lon, 7 patients with colon–prostate, 6 patients with tients with skin–lung, and 4 patients with colon– breast–ovary, 5 patients with lung–kidney, 5 pa- lung were detected (Table 2). 48 North Clin Istanb Table 3. Univariate variables evaluation for survival analysis All Synchronous Metachronous Median survival p Median survival p Median survival p (95% CI) (95% CI) (95% CI) Age, year <60 22.1 (12.5–31.8) 0.64 5.1 (1.0–16.4) 0.45 34.4 (1.2–67.6) 0.83 ≥60 24.9 (16.1–33.8) 8.9 (4.2–13.6) 35.9 (27.4–44.5) Gender Male 21.5 (14.9–28.2) 0.17 7.9 (2.1–13.8) 0.59 34.2 (26.1–42.2) 0.56 Female 39.8 (22.9–56.7) 10.7 (0.6–20.7) 44.7 (23.7–65.7) Smoking Yes 21.5 (14.7–28.3) 0.42 7.9 (2.3–13.6) 0.87 34.8 (20.9–48.7) 0.62 No 33.4 (17.9–48.9) 10.7 (0.1–24.1) 35.9 (21.3–50.6) Alcohol Yes 24.9 (15.2–34.6) 0.45 6.1 (3.8–8.4) 0.93 48.9 (24.7–73.1) 0.23 No 22.1 (15.6–28.6) 8.9 (2.9–14.9) 34.4 (25.4–43.3) Primarytumour site Breast 86.2 (79.4–93.1) 0.004 – 0.05 86.2 (79.4–93.1) 0.03 Larynx 19.3 (12.4–26.2) 8.9 (6.8–11.1) 28.7 (0.1–116.2) Colon 22.1 (8.8–35.4) 30.7 (0.1–62.8) 22.1 (7.3–37.1) Lung 22.2 (0.9–43.5) 2.1 (0.1–59) 34.2 (17.5–50.8) Esophagus 3.9 (2.8–5.8) 3.9 (0.1–5.2) 20.7 (0.1–23.1) Primarytumour histology Adenocancer 24.9 (15.5–34.3) 0.98 6.6 (0.1–1.41) 0.96 34.4 (21.2–47.6) 0.43 Squamouscell 22.2 (11.8–32.50) 8.9 (0.1–21.5) 34.8 (29.4–40.3) Others* 13.5 (0.4–26.5) 5.3 (0.1–13.4) 48.9 (0.1–49.1) Primarytumour stage Localized 29.6 (18.7–40.5) 0.001 12.1 (7.7–16.4) 0.01 41.1 (25.1–57.1) 0.09 Metastatic 15.7 (4.9–26.4) 5.3 (3.3–7.2) 28.7 (18.7–38.7) Primarytumour treatment Non–curative 13.7 (3.7–23.8) 0.005 5.1 (3.7–6.3) 0.001 26.4 (19.4–33.4) 0.36 Curative 30.7 (20.1–41.3) 16.1 (9.9–22.3) 41.1 (27.5–54.6) Ninety of 180 patients with double primary tu- did not use alcohol. Also, it was 21.5 months (95% mors died. The median survival was calculated as CI 14.7–28.3) in smokers and 33.4 months (95% 23.7 months [95% cond fi ence interval (CI) 16.7– CI 17.9–48.9) (p=0.42) in nonsmokers. The me - 30.7]. When the median survival was compared ac- dian survival in those whose primary tumor organ cording to gender, it was detected as 21.5 months was breast, colon, larynx, pancreas, and esophagus (95% CI 14.9–28.2) in males and 39.8 months was calculated as 86.2, 22.2, 22.1, 19.3, 6.6, and 3.9 (95% CI 22.9–56.7) in females (p=0.17). The me - months, respectively. The survival rate of the pa - dian survival was calculated as 22.1 months in alco- tients with primary tumor histology as an adeno- hol users (95% CI 15.6–28.6) (p=0.45), whereas it carcinoma and a squamous cell carcinoma was24.9 was 24.9 months (95% CI 15.2–34.6) in those who months (95% CI 15.5–34.3) and 22.3 months (95% Gokyer et al., Clinical features of the patient with multiple primary tumors 30.7 months (95% CI 20.1–41.3) and 13.7 months Table 4. Multivariable analysis of prognostic factors for (95% CI 3.7–23.8) in the patients who received a survival in patients with multiple primary tumours curative therapy and those who did not receive a cu- rative therapy, respectively (p=0.005). The median RR 95% CI p survival of co-occurrenceof synchronous tumors Age, ≥60 years 0.561 0.226–1.392 0.21 and metachronous tumors was 8.9 months (95% CI Gender, male 0.320 0.059–1.736 0.19 3.4–14.5) and 35.9 months (95% CI 27.6–44.3), Primarytumour site respectively (p<0.001). Colon 2.451 0.649–9.258 0.18 Univariate analyses showed that the primary Lung 2.710 0.876–8.377 0.08 site, stage, and status of receiving curative therapy of Larynx 2.163 0.669–6.995 0.19 the tumor could be used to predict patient survival Primarytumour stage (Table 3). Multivariate analysis showed that the Metastatic 2.837 1.075–7.490 0.03 presence of a synchronous tumor and a primary tu- Primarytumour treatment morat the metastatic stage wasassociated with poor Non-curative 0.850 0.236–3.064 0.81 prognosis and shorter survival in patients with two Multipleprimary status Synchronous 4.582 2.085–10.070 <0.001 primary tumors (Table 4 and Figure 2). CI: Confidence interval; RR: Relative risk. DISCUSSION The prevalence of multiple primary tumors increas- Survial es in relation to several factors such as increase in the number of treatment options, the fact that the pro- Synchronous 1.0 gression of some cancer cells becomes similar with Metachronous some chronic disease patterns, and increase in the 0.8 use of cytotoxic agents and ionized radiation [5–7]. The number of patients with secondary tumors- may also increase with the increase in the number 0.6 of cancer patients in the following years. Therefore, extreme caution is required regarding the develop- ment of secondary tumors in the patients who are followed up and treated for primary tumors. Both having an accompanying synchronous tumor and 0.2 the presence of a primary tumor at the metastatic p<0.001 stage were associated with bad prognosis in terms of survival in the present study. 0 50.0 100.0 150.0 200.0 250.0 300.0 Studies on multiple primary tumors available Months in the literature are generally retrospective stud- ies. They are especially based on the Warren and Figure 2. Survival rate of patients with synchronous Gates criterion and conducted by classifying pa- and metachronous tumors. tients as synchronous and metachronous [8]. The prevalence of multiple primary tumors was re- CI 11.8–32.5), respectively (p=0.06). The median ported as 0.73% in the study by Haddow et al. [9] survival rate in the patients with a primary organ- conducted with 58,333 cancer patients in 1972, limited and metastatic tumors was29.7 months 3.97% in the study by Storm et al. [10] conducted (95% CI 18.7–40.5) and 15.7 months (95% CI with 379,941 cancer patients in 1985, and 1.03% 4.9–26.4), respectively (p=0.001). The rate was in the study by Aydiner et al. [11] conducted with Cumulative survial 50 North Clin Istanb 26,000 cancer patients in 2000.This rate was 1.9% the increased risk of endometrial cancer. Since the in the present study. This variation might be due mutation analysis was not conducted, the assess- to dier ff ent strategies used in defining etiological ment might not be accurate. Gene mutation screen- causes and diagnoses of tumors. ing might be useful in patients detected with tumor co-occurrence in the future. Smoking seems to be an important risk factor for the development of multiple primary tumors [12]. When all these data were analyzed, it was The statistically signic fi ant rate of smoking in the foundthat metachronous tumors were more likely synchronous and metachronous groups was 47% to have higher survival rates, such as breast, prostate, and 34%, respectively, in the study by Aydiner et al. and colon. The association between smoking and al- [11]. The rate of cigarette smokers in the synchro - cohol use was weaker in metachronous tumors than nous and metachronous groups was 67% and 51%, in synchronous tumors. As a result, the survival rate respectively, in the present study. Hence, it can be was signic fi antly higher in metachronous tumors in concluded that smoking is an important risk factor the present study. for the development of synchronous tumors. Espe- Limited data are available in the literature on cially, a strong correlation exists between squamous the progression and treatment of multiple prima- cell carcinomas and cigarette smoking. The rate of ry tumors. In the study by Irimie et al. conducted smoking was found to be signic fi antly high in tu- with 62 cases with double primary tumors, it was mors known to be related to smoking, such as lung, found that curative surgery was applied to 40% of larynx, kidney, bladder, and pancreas. The patients the first primary synchronous tumors, whereas it who had a smoking history lived about 12 months could only be applied to 30% of the secondary less compared with nonsmokers, although the sur- tumors [15]. In the same study, it was found that vival rate was not statistically signic fi ant. only 10% of metachronous tumors could under- Alcohol use is a well-defined factor in the etiol- go curative surgery. Further, 57% of the first pri - ogy of cancers such as liver, esophagus, breast, and mary synchronous tumors were detected at the colorectal [13]. The patient data about alcohol use organ-limited stage and curative treatments were could not be accessed due to registry failure in many applied to the all of them. However, the rate of studies about the development of multiple tumors., treatment application to the first primary meta - Alcohol use did not make a meaningful dier ff ence chronous tumors was 80%. This result explained in terms of survival in the present study. However, the dier ff ence between the survival rates of syn - chronous and metachronous tumors. The sur - since the amount of alcohol usedcould not be as- sessed clearly, this issue wasc onsidered as a weak vival rate of patients with organ-limited primary point in data evaluation. tumor, who could undergo curative surgery, was significantly longer. When the data was analyzed for co-occurrence, head and neck–lung and colon–lung were the The present study had some limitations such as a most relevant co-occurrences among synchronous retrospective design, lack of gene mutation analyses, tumors. The most frequent co-occurrences in the and homogeneity of the patient population. If quan- study by Feng Li et al. conducted with 175 lung titative data could have been presented (as number cancer patients with double primary tumors, were of pack-years of smoking) its prognostic ee ff ct would lung–colon, lung–bladder, lung–breast, and lung– have been more accurately evaluated. esophagus [14]. Therefore, if the same tumor is In conclusion, the present study showed that detected in these organs, the possibility of having a synchronous and metastatic statuses of the disease second primary tumor should be considered before are independent risk factors for mortality. In the the diagnosis of metastasis. light of this information, a secondary cancer follow- Breast–endometrium co-occurrence may be the up may be informative, especially in the patients result of hormone therapy for breast cancer, due to with malignancy. Gokyer et al., Clinical features of the patient with multiple primary tumors Conflict of Interest: None declared. consumption in relation to the development of multiple primary cancers. Cancer 1977;40:1872–8. Financial Disclosure: The authors declared that this study 8. Warren S, Gates O. Multiple primary malignant tumors: a has received no financial support. survey of the literature and statistical study. Am J Cancer Authorship contributions: Concept – A.G.; Design – O.K.; 1932;16:1358–414. Supervision – I.C., S.U.; Material – I.C., O.K.; Data collection 9. Haddow AJ, Boyd JF, Graham AC. Multiple primary neoplasms or processing – A.G., H.K., B.E., E.T., M.B.H., I.H., O.K.; Analy- in the Western Hospital Region, Scotland: a survey based on sis – B.E., O.K.; Literature search – A.G.; Writing – A.G.; O.K.; Critical review – I.C., S.U., B.E. cancer registration data. Scott Med J 1972;17:143–52. 10. Storm HH, Jensen OM, Ewertz M, Lynge E, Olsen JH, Schou G, et al. Summary: multiple primary cancers in Denmark, 1943- REFERENCES 80. Natl Cancer Inst Monogr 1985;68:411–30. 11. Aydiner A, Karadeniz A, Uygun K, Tas S, Tas F, Disci R, et al. 1. Tachimori Y. Cancer screening in patients with cancer. Jpn J Clin Multiple primary neoplasms at a single institution: dier ff ences Oncol 2002;32:118–9. between synchronous and metachronous neoplasms. Am J Clin 2. Demandante CG, Troyer DA, Miles TP. Multiple primary ma- Oncol 2000;23:364–70. lignant neoplasms: case report and a comprehensive review of the 12. Leon ME, Peruga A, McNeill A, Kralikova E, Guha N, Minozzi literature. Am J Clin Oncol 2003;26:79–83. th S, et al. European Code against Cancer, 4 Edition: Tobacco and 3. Suzuki T, Takahashi H, Yao K, Inagi K, Nakayama M, Ma- cancer. Cancer Epidemiol 2015;39 Suppl 1:S20–33. koshi T, et al. Multiple primary malignancies in the head and 13. Williams LA, Olshan AF, Tse CK, Bell ME, Troester MA. Al- neck: a clinical review of 121 patients. Acta Otolaryngol Suppl cohol intake and invasive breast cancer risk by molecular subtype 2002;88–92. and race in the Carolina Breast Cancer Study. Cancer Causes 4. Ng AK, Kenney LB, Gilbert ES, Travis LB. Secondary malignan- Control 2016;27:259–69. cies across the age spectrum. Semin Radiat Oncol 2010;20:67–78. 14. Li F, Zhong WZ, Niu FY, Zhao N, Yang JJ, Yan HH, et al. Mul- 5. Hemminki K, Boe ff tta P. Multiple primary cancers as clues to tiple primary malignancies involving lung cancer. BMC Cancer environmental and heritable causes of cancer and mechanisms of carcinogenesis. IARC Sci Publ 2004;289–97. 2015;15:696. 6. Carey TE. Field cancerization: are multiple primary cancers 15. Irimie A, Achimas-Cadariu P, Burz C, Puscas E. Multiple pri- monoclonal or polyclonal? Ann Med 1996;28:183–8. mary malignancies--epidemiological analysis at a single tertiary 7. Wynder EL, Mushinski MH, Spivak JC. Tobacco and alcohol institution. J Gastrointestin Liver Dis 2010;19:69–73. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Northern Clinics of Istanbul Pubmed Central

Clinical features of the patient with multiple primary tumors: Single center experience

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Copyright: © 2017 by Istanbul Northern Anatolian Association of Public Hospitals
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10.14744/nci.2017.67044
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Abstract

Orıgınal Article MEDICAL ONCOLOGY North Clin Istanb 2017;4(1):43–51 doi: 10.14744/nci.2017.67044 Clinical features of the patient with multiple primary tumors: Single center experience 1 2 2 2 2 Ali Gokyer, Osman Kostek, Muhammet Bekir Hacioglu, Bulent Erdogan, Hilmi Kodaz, 2 2 2 2 Esma Turkmen, Ilhan Hacibekiroglu, Sernaz Uzunoglu, Irfan Cicin Department of Internal Medicine, Trakya University Faculty of Medicine, Edirne, Turkey Division of Medical Oncology, Department of Internal Medicine, Trakya University, Balkan Oncology Hospital, Edirne, Turkey ABSTRACT OBJECTIVE: Multiple primary tumors are the ones that develop in the same patient at the same or different times. They are usually examined under two groups. If the second tumor is diagnosed 6 months after the first tumor is diagnosed, it is named as metachronous tumor. If it is diagnosed in 6 months after the first diagnosis, it is called as synchronous tumor. The malignancy of tumors should be proved histologically. At least 2 cm of solid tissue should be present between two tumors. If they are at localized at the same place, a gap of at least 5 years should be present between them. Metastatic disease should be eliminated.This study aimedto review the clinical, demographic, and pathological features of multiple primary tumors, detect the prevalence, compare the results with literature findings, and evaluate and improve the approach to multiple primary tumors. METHODS: A total of 170 patients diagnosed with multiple primary tumors were included in this study. Patient data were obtained from pathology and medical reports of the patients. RESULTS: Most of the multiple primary tumors were metachronous. The number of male patients was more than that of female patients. The median time between double tumors was 3 monthsforsynchronous tumorsand 26 months for metachronous tumors. Synchronous tumors with the highest prevalence of comorbidity were lung–lar- ynx and lung–colon, whereas metachronous tumors with the highest prevalence of comorbidity were lung–blad- der, lung–larynx, breast–endometrium, and breast–colon. The history of smoking and alcohol was found to be higher in male patients andsynchronous tumors. CONCLUSION: The detection of the first tumor in the metastatic stage and an accompanying synchronous sec - ondary tumor was found to be a poor prognostic factor. The treatment of the first tumor, smoking, squamous cell histology, and male gender were among the other factors negatively affecting survival,although they were not statistically significant. Keywords: Metachronous; multiple primary tumors; survival; synchronous. ultiple primary tumors are the ones that dier ff ent times,accounting for 0.7%–11% of all car - Mdevelop in the same patient at the same or cinomas [1, 2]. If the second tumor is diagnosed Received: January 09, 2017 Accepted: April 05, 2017 Online: May 10, 2017 Correspondence: Dr. Osman KOSTEK. Trakya Universitesi, Ic Hastaliklari Anabilim Dali, Tıbbi Onkoloji Bilim Dali, Balkan Onkoloji Hastanesi, Edirne, Turkey. Tel: +90 284 - 235 76 41-1851 e-mail: [email protected] © Copyright 2017 by Istanbul Northern Anatolian Association of Public Hospitals–Available online at www.kuzeyklinikleri.com 44 North Clin Istanb 6 months after the first tumor is diagnosed, it is A total of 10.000 files related to patients with cancer named as metachronous tumor, whereas if it is di- diagnosis were evaluated agnosed in 6 months after the first diagnosis, it is called as synchronous tumor [3]. The formation 190 patients with of the second tumor occurs as a result of a series multiple primary tumor of complex interactions. The first tumor increases the risk of developing secondary tumor [4]. Also, 10 patients smoking, alcohol intake, environmental factors, and with BCC were excluded genetic mutations increase the risk of developing secondary tumor. The chances of developing sec- 180 subjects were ondary tumorsare increased by additive and syner- included to the study gistic ee ff ct of the treatment with combined chemo - therapy and radiotherapy applications. All patients 49 patients with 121 patients with should undergo special surveillance and should be Synchronous tumor Metachronous tumor followedup and treated with methods such as pro- phylactic surgery if necessary. Figure 1. Method of selection of patient group. This studyaimed to evaluate the clinical, de - mographic, and pathological features of multiple coexistence of double tumors and their fates, diag- primary tumors,and compare the results with lit- nosis date of the tumors, and dier ff ence between erature findings. The findings might contribute to their diagnosis dates in months was recorded. Tu- future approaches to multiple primary tumors. mor stage was considered as metastatic disease and organ-limited disease. The smoking history of the MATERIALS AND METHODS patient was identiefi d as having a cigarette story or not smoking. The tissue diagnoses in pathol- Patient features ogy reports were noted. Tumor treatment options This was a retrospective descriptive case series were obtained from follow-up and treatment files. study, and all the cases with cancer diagnosis in the Treatment options were also categorized as cura- Trakya University medical oncology department tive and noncurative. If the secondtumor is diag- between 2005 and 2015 were evaluated retrospec- nosed 6 months after the first tumor is diagnosed, tively. The medical recordsof 10,000 patients were it is named as metachronous tumor, whereas if it is analyzed before the study. The medical records of diagnosed in 6 months after the first diagnosis, it 180 patients with multiple primary tumors were in- is called as synchronous tumor. Also, each tumor cluded in the study. The patients with basal cell skin with tissue biopsies was shown to be malignant carcinoma as one of the tumors,out of 10 patients with clinical and histological features, indicating with multiple primary tumors, were excluded from that these tumors did not occur due to recurrence the study (Figure 1). or metastasis of other tumors. The cases without tissue diagnosis or the ones with tissue diagno- Study design sis whose tumor could not be shown as malignant The age and sex of the patients, history of smoking with immunohistological and/or histopathological and alcohol use, age of first tumor diagnosis, first staining were not included in this study. The fate of tumor organ, first tumor histology, first tumor site, the patients was given as dead or being followedup. first tumor stage, first tumor treatment, second tu - The present age of the patients who were being fol- mor age, second tumor organ, second tumor histol- lowedup was determined. The age on the death date ogy, second tumor site, second tumor stage, second and the death date were also determined for the tumor treatment, synchronous and metachronous dead patients. Based on the pathology reports, the Gokyer et al., Clinical features of the patient with multiple primary tumors exact diagnosis dates of the first and second tumors colon (10), lung (9), larynx (6), prostate (4), skin (4), were recorded. The time between these two dates breast (3), bladder (3), endometrium (3), pancreas was recorded in months.Medical oncology records, (2), stomach (2), thyroid (1), ovary (1), esophagus hospital files, automation system, and pathology (1). Thirty-three (67.3%) of these tumors had ad- laboratory records were used during data collection. enocarcinoma histology, 14 (28.6%) had squamous The information on the recent status of the patients cell carcinoma histology, 1had follicular carcinoma, who had at least 6 months over their last follow- and 1had melanoma histology. Twenty-one patients up was provided by phone. The death records were (42.9%) had metastatic disease, and 28 patients obtained from the Ministry of Health death noti- (57.1%) had organ-limited disease. c fi ation system. The date of diagnosis was taken as The prevalence order of the origin of second- the time of the pathologic diagnosis or the time of ary tumorin the patients with synchronous tumor surgery in patients without preoperative diagnosis. waslungs (15), colon (10), kidney (5), bladder (4), prostate (3), ovary(3), larynx (3), pancreas (2), en- Statistical analysis dometrium (1), and stomach (1). Thirty-eight of these tumors (76.6%) had adenocarcinoma histol- Univariate and multivariate analyses were per- ogy, and 11 tumors (22.4%) had squamous cell car- formed. Mean and median values of the patients cinoma histology. Twenty-two patients (44.9%) had were determined by descriptive statistics. Standard metastatic disease, whereas27 patients (55.1%) had deviation (±) was used. The parametric variables organ-limited disease. were compared between groups using theindepen- dent-samplet test. Nonparametric variables were Twenty-nine (59.2%) of the patients with syn- evaluated using the chi-square test. Kaplan–Meier chronous tumor died, and 20 patients (40.8%) car- method was used for survival analyses. The confi- ried on with their clinical follow-ups. When the dence interval was considered as 95%, and a p value co-occurrence of double tumors was analyzed in less than 0.05 was considered as statisticallysignifi- months, the mean was 2.63±1.56 (median 3; range cant. All data were entered in SPSS 20.0 for Win- 0–6). Co-occurrence was most frequently detected dows (SPSS; Chicago, IL, USA). in five patients with colon–lung and fivepatients with lung–laryngeal (Table 2). RESULTS One hundred and twenty-one patients with metachronous tumors were detected. Forty- Study group features nine of these patients were female (40.5%) and The prevalence of multiple primary tumors was 72male (59.5%). The mean age of the patients was 1.9% in all patients. The patients were basically di- 62±12.13 years (median 63 years; range 36–89 vided into two groups: ones with synchronous and years). Thirty patients (24.8%)drank alcohol, and metachronous tumors. Further, 49 patients (28%) 91 patients (75.2%) did not drink alcohol. Of the hadsynchronous tumors and 121 patients (72%) patients, 61 (50.4%) had smoking history and 60 hadmetachronous tumors (Figure 1). (49.6%) of them did notsmoke. The clinical and demographic data of the pa - The mean age of primary tumor in patients with tients areshown in Table 1. The rate of smoking was metachronous tumors was 56±13.00 (median 57, signicfi antly higher in patients with synchronous range 20–88). According to the prevalence order tumorsthan in patients with metachronous tumors. of the tumor source, tumorswere detected in the Similarly, the rates of metastatic disease were high- breast (25), colon (16), larynx (16), bladder (12), erin patients with synchronous tumors than in pa- prostate (9), skin (8), endometrium (8), lungs (7), tients with metachronous tumors (Table 1). kidney (6), ovary (5), testis (2), stomach (2), thyroid The prevalence order of the origin of primary (1), nose (1), esophagus (1), liver (1), and cervix (1). tumor in the patients with synchronous tumorswas Of these tumors, 89 had adenocarcinoma histology 46 North Clin Istanb Table 1. Clinical and demographic characteristics of subjects Synchronous tumour Metachronous tumour (n=49) (n=121) n % n % Age, year 64±12 62±12 Gender, M/F 11/38 49/72 Smoking* 33 67.3 61 50.4 Alcoholconsumption 13 26.5 30 24.8 Histopathology of primarytumour, Adenocancer 33 67.3 89 73.5 Squamouscellcancer 14 28.6 29 24.0 Others** 2 4.1 3 2.5 Stage of primarytumour** Localized 28 57.1 97 80.2 Metastatic 21 42.9 24 19.8 Histopathology of secondarytumour Adenocancer 38 76.6 94 77.6 Squamouscellcancer 11 22.4 26 21.4 Stage of secondarytumour Localized 27 55.1 69 57.1 Metastatic 21 44.9 52 42.9 Time intervalbetweensecondtumour (month)** Median (Interquartile range) 3 (1–4) 26 (13–68) Minimum- maximum 0–6 7–312 Clinicaloutcome Death 29 59.2 61 50.4 *p<0.05; **Insynchronous tumours, 1 patient had tyroid follicular cancer and the other patient had malign melanoma. In metachronous group, 2 patients had pure seminoma, theother had thyroid follicular cancer. (73%), 29 had squamous cell carcinoma histology carcinoma histology (77.7%), 26 had squamous cell (24%), 2 had seminoma histology (1.7%) and 1 had carcinoma histology (21.5%), and 1 had follicular follicular cancer histology. Twenty-four patients cancer histology. Sixty-nine patients (57%) had (19.8%) had metastatic disease, whereas 97 patients metastatic disease, and 52 patients (43%) had an (80.2%) had an organ-limited disease. organ-limited disease. The mean age of the secondary tumor in pa - Of patients with a metachronous disease, 61 tients with metachronous tumors was 60±12.8 patients (50.4%) died and 60 patients (49.6%) years (median 61; range 34–89). The tumors were continued with their treatment in the outpatient classie fi d according to the prevalence orderas lung clinic.The mean age of the co-occurrence of double (35), colon (21), breast (9), bladder (8), endome- tumors in months was 50±60.26 months (median trium (8), prostate (7), kidney (6), larynx (6), pan- 26months; range 7–312 months). In terms of tu- creas (3), skin (3), stomach (2), tongue (2), thyroid mor co-occurrence, 10 patients with lung–blad- (2), esophagus (1), biliary tract (1), and ureter (1) der, 10 patients with larynx–lung, 9 patients with (Table 2). Ninety-four of these tumors had adeno- breast–endometrium, 8 patients with breast–co- Gokyer et al., Clinical features of the patient with multiple primary tumors Table 2. Tumours location in patients with multiple primary tumours related to their organ involvement Synchronous Metachronous Synchronous Metachronous tumour (n=49) tumour (n=49) tumour (n=49) tumour (n=49) Colon, n (count) Larynx – 1 Lung 5 4 Stomach, n (count) Kidney 3 1 Pancreas 1 – Endometrium 3 2 Prostat 1 – Colon 2 – Endometrium – 1 Prostat 2 – Tongue – 1 Bladder 1 3 Kidney, n (count) Skin 1 1 Thyroid 1 – Larynx 1 – Lung – 3 Ovary – 2 Colon – 1 Stomach – 1 Skin – 1 Lung, n (count) Bladder – 1 Larynx 5 – Breast, n (count) Pancreas 3 – Colon – 7 Skin 3 – Endometrium – 5 Bladder 2 4 Ovary – 4 Kidney 1 2 Breast – 3 Stomach 1 – Kidney – 2 Breast 1 – Thyroid – 2 Prostat 1 1 Lung – 2 Ovary 1 – Endometrium, n (count) Larynx, n (count) Breast – 4 Lung – 9 Lung – 3 Prostat 1 3 Colon – 2 Skin 1 1 Prostat, n (count) Bladder 1 – Colon – 6 Pancreas – 2 Larynx – 2 Tongue – 1 Lung – 1 Bladder, n (count) Skin, n (count) Lung – 6 Lung – 5 Prostat 2 2 Breast – 1 Skin 1 – Colon – 1 Larynx – 2 Esophagus, n (count) Colon – 2 Lung – 1 Ovary, n (count) Thyroid, n (count) Breast 2 1 Kidney – 1 Endometrium 1 – Testis, n (count) Colon – 2 Lung – 1 Pancreas – 1 Ureter – 1 lon, 7 patients with colon–prostate, 6 patients with tients with skin–lung, and 4 patients with colon– breast–ovary, 5 patients with lung–kidney, 5 pa- lung were detected (Table 2). 48 North Clin Istanb Table 3. Univariate variables evaluation for survival analysis All Synchronous Metachronous Median survival p Median survival p Median survival p (95% CI) (95% CI) (95% CI) Age, year <60 22.1 (12.5–31.8) 0.64 5.1 (1.0–16.4) 0.45 34.4 (1.2–67.6) 0.83 ≥60 24.9 (16.1–33.8) 8.9 (4.2–13.6) 35.9 (27.4–44.5) Gender Male 21.5 (14.9–28.2) 0.17 7.9 (2.1–13.8) 0.59 34.2 (26.1–42.2) 0.56 Female 39.8 (22.9–56.7) 10.7 (0.6–20.7) 44.7 (23.7–65.7) Smoking Yes 21.5 (14.7–28.3) 0.42 7.9 (2.3–13.6) 0.87 34.8 (20.9–48.7) 0.62 No 33.4 (17.9–48.9) 10.7 (0.1–24.1) 35.9 (21.3–50.6) Alcohol Yes 24.9 (15.2–34.6) 0.45 6.1 (3.8–8.4) 0.93 48.9 (24.7–73.1) 0.23 No 22.1 (15.6–28.6) 8.9 (2.9–14.9) 34.4 (25.4–43.3) Primarytumour site Breast 86.2 (79.4–93.1) 0.004 – 0.05 86.2 (79.4–93.1) 0.03 Larynx 19.3 (12.4–26.2) 8.9 (6.8–11.1) 28.7 (0.1–116.2) Colon 22.1 (8.8–35.4) 30.7 (0.1–62.8) 22.1 (7.3–37.1) Lung 22.2 (0.9–43.5) 2.1 (0.1–59) 34.2 (17.5–50.8) Esophagus 3.9 (2.8–5.8) 3.9 (0.1–5.2) 20.7 (0.1–23.1) Primarytumour histology Adenocancer 24.9 (15.5–34.3) 0.98 6.6 (0.1–1.41) 0.96 34.4 (21.2–47.6) 0.43 Squamouscell 22.2 (11.8–32.50) 8.9 (0.1–21.5) 34.8 (29.4–40.3) Others* 13.5 (0.4–26.5) 5.3 (0.1–13.4) 48.9 (0.1–49.1) Primarytumour stage Localized 29.6 (18.7–40.5) 0.001 12.1 (7.7–16.4) 0.01 41.1 (25.1–57.1) 0.09 Metastatic 15.7 (4.9–26.4) 5.3 (3.3–7.2) 28.7 (18.7–38.7) Primarytumour treatment Non–curative 13.7 (3.7–23.8) 0.005 5.1 (3.7–6.3) 0.001 26.4 (19.4–33.4) 0.36 Curative 30.7 (20.1–41.3) 16.1 (9.9–22.3) 41.1 (27.5–54.6) Ninety of 180 patients with double primary tu- did not use alcohol. Also, it was 21.5 months (95% mors died. The median survival was calculated as CI 14.7–28.3) in smokers and 33.4 months (95% 23.7 months [95% cond fi ence interval (CI) 16.7– CI 17.9–48.9) (p=0.42) in nonsmokers. The me - 30.7]. When the median survival was compared ac- dian survival in those whose primary tumor organ cording to gender, it was detected as 21.5 months was breast, colon, larynx, pancreas, and esophagus (95% CI 14.9–28.2) in males and 39.8 months was calculated as 86.2, 22.2, 22.1, 19.3, 6.6, and 3.9 (95% CI 22.9–56.7) in females (p=0.17). The me - months, respectively. The survival rate of the pa - dian survival was calculated as 22.1 months in alco- tients with primary tumor histology as an adeno- hol users (95% CI 15.6–28.6) (p=0.45), whereas it carcinoma and a squamous cell carcinoma was24.9 was 24.9 months (95% CI 15.2–34.6) in those who months (95% CI 15.5–34.3) and 22.3 months (95% Gokyer et al., Clinical features of the patient with multiple primary tumors 30.7 months (95% CI 20.1–41.3) and 13.7 months Table 4. Multivariable analysis of prognostic factors for (95% CI 3.7–23.8) in the patients who received a survival in patients with multiple primary tumours curative therapy and those who did not receive a cu- rative therapy, respectively (p=0.005). The median RR 95% CI p survival of co-occurrenceof synchronous tumors Age, ≥60 years 0.561 0.226–1.392 0.21 and metachronous tumors was 8.9 months (95% CI Gender, male 0.320 0.059–1.736 0.19 3.4–14.5) and 35.9 months (95% CI 27.6–44.3), Primarytumour site respectively (p<0.001). Colon 2.451 0.649–9.258 0.18 Univariate analyses showed that the primary Lung 2.710 0.876–8.377 0.08 site, stage, and status of receiving curative therapy of Larynx 2.163 0.669–6.995 0.19 the tumor could be used to predict patient survival Primarytumour stage (Table 3). Multivariate analysis showed that the Metastatic 2.837 1.075–7.490 0.03 presence of a synchronous tumor and a primary tu- Primarytumour treatment morat the metastatic stage wasassociated with poor Non-curative 0.850 0.236–3.064 0.81 prognosis and shorter survival in patients with two Multipleprimary status Synchronous 4.582 2.085–10.070 <0.001 primary tumors (Table 4 and Figure 2). CI: Confidence interval; RR: Relative risk. DISCUSSION The prevalence of multiple primary tumors increas- Survial es in relation to several factors such as increase in the number of treatment options, the fact that the pro- Synchronous 1.0 gression of some cancer cells becomes similar with Metachronous some chronic disease patterns, and increase in the 0.8 use of cytotoxic agents and ionized radiation [5–7]. The number of patients with secondary tumors- may also increase with the increase in the number 0.6 of cancer patients in the following years. Therefore, extreme caution is required regarding the develop- ment of secondary tumors in the patients who are followed up and treated for primary tumors. Both having an accompanying synchronous tumor and 0.2 the presence of a primary tumor at the metastatic p<0.001 stage were associated with bad prognosis in terms of survival in the present study. 0 50.0 100.0 150.0 200.0 250.0 300.0 Studies on multiple primary tumors available Months in the literature are generally retrospective stud- ies. They are especially based on the Warren and Figure 2. Survival rate of patients with synchronous Gates criterion and conducted by classifying pa- and metachronous tumors. tients as synchronous and metachronous [8]. The prevalence of multiple primary tumors was re- CI 11.8–32.5), respectively (p=0.06). The median ported as 0.73% in the study by Haddow et al. [9] survival rate in the patients with a primary organ- conducted with 58,333 cancer patients in 1972, limited and metastatic tumors was29.7 months 3.97% in the study by Storm et al. [10] conducted (95% CI 18.7–40.5) and 15.7 months (95% CI with 379,941 cancer patients in 1985, and 1.03% 4.9–26.4), respectively (p=0.001). The rate was in the study by Aydiner et al. [11] conducted with Cumulative survial 50 North Clin Istanb 26,000 cancer patients in 2000.This rate was 1.9% the increased risk of endometrial cancer. Since the in the present study. This variation might be due mutation analysis was not conducted, the assess- to dier ff ent strategies used in defining etiological ment might not be accurate. Gene mutation screen- causes and diagnoses of tumors. ing might be useful in patients detected with tumor co-occurrence in the future. Smoking seems to be an important risk factor for the development of multiple primary tumors [12]. When all these data were analyzed, it was The statistically signic fi ant rate of smoking in the foundthat metachronous tumors were more likely synchronous and metachronous groups was 47% to have higher survival rates, such as breast, prostate, and 34%, respectively, in the study by Aydiner et al. and colon. The association between smoking and al- [11]. The rate of cigarette smokers in the synchro - cohol use was weaker in metachronous tumors than nous and metachronous groups was 67% and 51%, in synchronous tumors. As a result, the survival rate respectively, in the present study. Hence, it can be was signic fi antly higher in metachronous tumors in concluded that smoking is an important risk factor the present study. for the development of synchronous tumors. Espe- Limited data are available in the literature on cially, a strong correlation exists between squamous the progression and treatment of multiple prima- cell carcinomas and cigarette smoking. The rate of ry tumors. In the study by Irimie et al. conducted smoking was found to be signic fi antly high in tu- with 62 cases with double primary tumors, it was mors known to be related to smoking, such as lung, found that curative surgery was applied to 40% of larynx, kidney, bladder, and pancreas. The patients the first primary synchronous tumors, whereas it who had a smoking history lived about 12 months could only be applied to 30% of the secondary less compared with nonsmokers, although the sur- tumors [15]. In the same study, it was found that vival rate was not statistically signic fi ant. only 10% of metachronous tumors could under- Alcohol use is a well-defined factor in the etiol- go curative surgery. Further, 57% of the first pri - ogy of cancers such as liver, esophagus, breast, and mary synchronous tumors were detected at the colorectal [13]. The patient data about alcohol use organ-limited stage and curative treatments were could not be accessed due to registry failure in many applied to the all of them. However, the rate of studies about the development of multiple tumors., treatment application to the first primary meta - Alcohol use did not make a meaningful dier ff ence chronous tumors was 80%. This result explained in terms of survival in the present study. However, the dier ff ence between the survival rates of syn - chronous and metachronous tumors. The sur - since the amount of alcohol usedcould not be as- sessed clearly, this issue wasc onsidered as a weak vival rate of patients with organ-limited primary point in data evaluation. tumor, who could undergo curative surgery, was significantly longer. When the data was analyzed for co-occurrence, head and neck–lung and colon–lung were the The present study had some limitations such as a most relevant co-occurrences among synchronous retrospective design, lack of gene mutation analyses, tumors. The most frequent co-occurrences in the and homogeneity of the patient population. If quan- study by Feng Li et al. conducted with 175 lung titative data could have been presented (as number cancer patients with double primary tumors, were of pack-years of smoking) its prognostic ee ff ct would lung–colon, lung–bladder, lung–breast, and lung– have been more accurately evaluated. esophagus [14]. Therefore, if the same tumor is In conclusion, the present study showed that detected in these organs, the possibility of having a synchronous and metastatic statuses of the disease second primary tumor should be considered before are independent risk factors for mortality. In the the diagnosis of metastasis. light of this information, a secondary cancer follow- Breast–endometrium co-occurrence may be the up may be informative, especially in the patients result of hormone therapy for breast cancer, due to with malignancy. Gokyer et al., Clinical features of the patient with multiple primary tumors Conflict of Interest: None declared. consumption in relation to the development of multiple primary cancers. Cancer 1977;40:1872–8. Financial Disclosure: The authors declared that this study 8. Warren S, Gates O. Multiple primary malignant tumors: a has received no financial support. survey of the literature and statistical study. Am J Cancer Authorship contributions: Concept – A.G.; Design – O.K.; 1932;16:1358–414. Supervision – I.C., S.U.; Material – I.C., O.K.; Data collection 9. Haddow AJ, Boyd JF, Graham AC. Multiple primary neoplasms or processing – A.G., H.K., B.E., E.T., M.B.H., I.H., O.K.; Analy- in the Western Hospital Region, Scotland: a survey based on sis – B.E., O.K.; Literature search – A.G.; Writing – A.G.; O.K.; Critical review – I.C., S.U., B.E. cancer registration data. Scott Med J 1972;17:143–52. 10. Storm HH, Jensen OM, Ewertz M, Lynge E, Olsen JH, Schou G, et al. Summary: multiple primary cancers in Denmark, 1943- REFERENCES 80. Natl Cancer Inst Monogr 1985;68:411–30. 11. Aydiner A, Karadeniz A, Uygun K, Tas S, Tas F, Disci R, et al. 1. Tachimori Y. Cancer screening in patients with cancer. Jpn J Clin Multiple primary neoplasms at a single institution: dier ff ences Oncol 2002;32:118–9. between synchronous and metachronous neoplasms. Am J Clin 2. Demandante CG, Troyer DA, Miles TP. Multiple primary ma- Oncol 2000;23:364–70. lignant neoplasms: case report and a comprehensive review of the 12. Leon ME, Peruga A, McNeill A, Kralikova E, Guha N, Minozzi literature. Am J Clin Oncol 2003;26:79–83. th S, et al. European Code against Cancer, 4 Edition: Tobacco and 3. Suzuki T, Takahashi H, Yao K, Inagi K, Nakayama M, Ma- cancer. Cancer Epidemiol 2015;39 Suppl 1:S20–33. koshi T, et al. Multiple primary malignancies in the head and 13. Williams LA, Olshan AF, Tse CK, Bell ME, Troester MA. Al- neck: a clinical review of 121 patients. Acta Otolaryngol Suppl cohol intake and invasive breast cancer risk by molecular subtype 2002;88–92. and race in the Carolina Breast Cancer Study. Cancer Causes 4. Ng AK, Kenney LB, Gilbert ES, Travis LB. Secondary malignan- Control 2016;27:259–69. cies across the age spectrum. Semin Radiat Oncol 2010;20:67–78. 14. Li F, Zhong WZ, Niu FY, Zhao N, Yang JJ, Yan HH, et al. Mul- 5. Hemminki K, Boe ff tta P. Multiple primary cancers as clues to tiple primary malignancies involving lung cancer. BMC Cancer environmental and heritable causes of cancer and mechanisms of carcinogenesis. IARC Sci Publ 2004;289–97. 2015;15:696. 6. Carey TE. Field cancerization: are multiple primary cancers 15. Irimie A, Achimas-Cadariu P, Burz C, Puscas E. Multiple pri- monoclonal or polyclonal? Ann Med 1996;28:183–8. mary malignancies--epidemiological analysis at a single tertiary 7. Wynder EL, Mushinski MH, Spivak JC. Tobacco and alcohol institution. J Gastrointestin Liver Dis 2010;19:69–73.

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Published: May 10, 2017

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