|Year : 2016 | Volume
| Issue : 4 | Page : 595-599
Second primary malignancy: A retrospective analysis report from a tertiary cancer center of North India
D Sharma, G Singh, N Kakkar, S Raj
Department of Radiation Oncology, VMMC and Safdarjung Hospital, New Delhi, India
|Date of Web Publication||21-Apr-2017|
Department of Radiation Oncology, VMMC and Safdarjung Hospital, New Delhi
Source of Support: None, Conflict of Interest: None
AIM OF STUDY: We analyzed the data of second primary malignancy (SPM) from one of the tertiary cancer centers of North India, and the basic aim was to retrieve incidence, prognosis, and outcomes. MATERIALS AND METHODS: A retrospective study was conducted in the Department of Radiation Oncology in a tertiary cancer center between January 1, 2011, and December 31, 2015. A total of 6000 cases of cancer were analyzed, out of which cases who presented with histological proven synchronous SPM were included in this study. RESULTS: The present study showed three cases (8.1%) of SPM who are attributed to field carcinogenesis. There were five cases in which metachronous malignancy develops in the previous radiation therapy field. There is 26% of synchronous malignancy as compared to 74% of metachronous malignancy. In the present study, most diagnosed synchronous malignancies were carcinoma breast, while in metachronous malignancies, carcinoma breast and gynecological cancers were most common. CONCLUSIONS: SPMs are not very rare. Hence, pretreatment and follow-up evaluation should be meticulous to rule out SPMs.
Keywords: Field carcinogenesis, metachronous, second primary malignancy, synchronous
|How to cite this article:|
Sharma D, Singh G, Kakkar N, Raj S. Second primary malignancy: A retrospective analysis report from a tertiary cancer center of North India. Indian J Cancer 2016;53:595-9
|How to cite this URL:|
Sharma D, Singh G, Kakkar N, Raj S. Second primary malignancy: A retrospective analysis report from a tertiary cancer center of North India. Indian J Cancer [serial online] 2016 [cited 2020 May 30];53:595-9. Available from: http://www.indianjcancer.com/text.asp?2016/53/4/595/204779
| » Introduction|| |
The incidence of double malignancy is not uncommon.,, Bugher in 1934 analyzed cases of double primary malignancies and derived an equation for the probability of death during a specified period with a new second malignancy.
The second primary malignancy (SPM) is defined as a second de novo malignant neoplasm with known cancer. An SPM can be synchronous or metachronous. Warren and Gates first gave the criteria used for the diagnosis of SPM.
Warren and Gates criteria for diagnosis of multiple primary malignancies are as follows.
- Each of the tumors must be malignant, each confirmed by histology
- Each must be geographically separate and distinct. The lesions should be separated by normal mucosa
- Probability of one being the metastasis of the other must be excluded.
An SPM can be synchronous or metachronous. When the SPM is diagnosed within 6 months of the primary tumor, it is known as synchronous malignancy and the term metachronous is used when the SPM is diagnosed more than 6 months after the diagnosis of the primary tumor. In literature, data regarding the occurrence and the outcome of SPM from the Indian subcontinent are limited. Hence, we present the data of SPM from one of the tertiary cancer centers from North India with a review of relevant literature.
| » Materials and Methods|| |
We conducted a retrospective observational study in the Department of Radiation Oncology in a tertiary cancer center between January 1, 2011, and December 31, 2015. A total of 6000 cases of cancer were analyzed, out of which cases who presented with histological proven synchronous and metachronous primary as per the Warren and Gates criteria were included in the study. Time interval which was taken to differentiate between synchronous and metachronous malignancies was 6 months.,, Details such as age of diagnosis of each tumor, sex, any family history, site of origin, histopathological and radiological imaging, whether the tumor was synchronous or metachronous, clinical staging, treatment received by patient, and status at last follow-up were recorded.
| » Results|| |
During a period of 5 years between January 1, 2011, and December 31, 2015, total of 6000 patients were registered, out of which 38 patients presented either with metachronous malignancy or with synchronous malignancy. In the present study, one patient presented with synchronous malignancy (carcinoma breast and urinary bladder cancer) and developed carcinoma cervix IIB after 7 years at as metachronous malignancy.
The most common site of primary malignancy is carcinoma breast (11 cases), followed by head and neck squamous cell carcinoma (HNSCC) (10 cases) [Figure 1] and [Figure 2].
A total of ten cases were diagnosed with synchronous malignancy. Out of these ten cases of synchronous malignancy, five were male and five were female. Median age of diagnosis was 58 years (range, 28–85 years) [Table 1].
A total of 29 cases were diagnosed with metachronous malignancy. Male-female ratio is 0.75. The median age for the primary tumor was 52 years (range, 25–76 years) and that for the metachronous malignancy was 59 years (range, 27–80 years). The median time interval between the primary and secondary malignancy was 5.5 years (range, 1–16 years) [Table 2].
| » Discussion|| |
The incidence of SPM is not uncommon; it is common for the last 100 years. The etiopathology of SPM can either be various genetic events or common environmental risk factor. SPMs have been associated with DNA microsatellite instability, for example, Lynch I and Lynch II syndromes. Carcinoma of breast, esophagus, and soft tissue has been associate with mutation in tumor suppressor genes such as p16, p53, PTEN, and Rb gene.
It has been found that the cumulative lifetime risk of SPM in HNSCC is 36%. This has been attributed to field carcinogenesis in response to exposure to risk factors such as tobacco, smoking, and alcohol consumption., In our study, there are three cases (8.1%) in which SPM is attributed to field carcinogenesis. Another cause of SPM is ionizing radiation. Various studies have shown that the risk of lung cancer, sarcoma increases with a radiation dose above 5 Gy. Such type of cancer usually occurs in the prior radiation field and usually after a latent period of ten or more years.,, In the present study, there are five cases in which metachronous malignancy develops in the previous radiation therapy field [Table 3].
SPM can occur at any age. Various studies done so far revealed that it is more common in old age.,,,, In the present study, the median age at the time of second tumor diagnosis is 59 years and 70% of patients with SPM were more than 50 years of age. In the reviewed literature, male/female ratio varies between 0.9 and 3.5, with male predominance.,, In the present study, the male: female ratio is 0.85.
The ratio of synchronous to metachronous malignancies differs in different studies. In a study by Aydiner et al., synchronous malignancy was 34% as compared to metachronous malignancy which was 66%. Flannery et al. reported 20% of synchronous and 80% of metachronous tumors in their SPM series. In the present study, there are 26% of synchronous malignancy as compared to 74% of metachronous malignancy. Usually, synchronous SPMs are seen in genitourinary and gastrointestinal systems., In the present study, most diagnosed synchronous malignancies were carcinoma breast; in metachronous malignancies, carcinoma breast and gynecological cancers were most common.
As per the SEER data results (1973–2003), the most common primary cancers in patients with SPM are breast carcinoma, prostate carcinoma, respiratory system and lung cancers, colorectal cancer, and urinary system cancers. In the present study, the most common primary tumors were carcinoma breast, HNSCC, gynecological cancers, gastrointestinal tract (GIT) malignancy In males, most common primary malignancies were HNSCC, GIT malignancy, and genitourinary malignancy and that in female were carcinoma breast and gynecological cancers. In other studies, most common tumors were carcinoma larynx, lung cancer, and breast cancer.,,
The possibility of SPM must always be considered while pretreatment evaluation. For early detection of SPM, screening procedures are useful, and this in turn will improve the outcome of the patients with SPM. However, the optimal screening modalities and strategies to reduce mortality from SPM remain to be defined for most tumor sites.
| » Conclusions|| |
SPM is not uncommon. It manifests either as synchronous or metachronous malignancy. The early diagnosis of SPM should not be missed during follow-up. And also, during follow-up, cancer patients should be informed the role of preventive medicine and encourage use of screening methods.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| » References|| |
Vaslamatzis M, Alevizopoulos N, Petraki C. Second primary neoplasms (SPN) in cancer patients. Proc ASCO 2003;22:3581.
Morgenfeld EL, Tognelli GF, Deza E, Santillan D, Ares S. Synchronous and metachronous second (ST) and third (TT) primary tumors in a large patient population. Proc ASCO 2003;22:3152.
Irimie A, Achimas-Cadariu P, Burz C, Puscas E. Multiple primary malignancies–epidemiological analysis at a single tertiary institution. J Gastrointestin Liver Dis 2010;19:69-73.
Bugher JC. The probability of the chance of accurence of multiple malignant neoplasms. Am J Cancer 1934;21:2309-824.
Warren S, Gates O. Multiple primary malignant tumors: A survey of the literature and statistical study. Am J Cancer 1932;16:1358-414.
Vaamonde P, Martín C, del Río M, LaBella T. Second primary malignancies in patients with cancer of the head and neck. Otolaryngol Head Neck Surg 2003;129:65-70.
Suzuki T, Takahashi H, Yao K, Inagi K, Nakayama M, Makoshi T, et al.
Multiple primary malignancies in the head and neck: A clinical review of 121 patients. Acta Otolaryngol Suppl 2002;547:88-92.
Morris LG, Sikora AG, Patel SG, Hayes RB, Ganly I. Second primary cancers after an index head and neck cancer: Subsite-specific trends in the era of human papillomavirus-associated oropharyngeal cancer. J Clin Oncol 2011;29:739-46.
Cheng HY, Chu CH, Chang WH, Hsu TC, Lin SC, Liu CC, et al.
Clinical analysis of multiple primary malignancies in the digestive system: A hospital-based study. World J Gastroenterol 2005;11:4215-9.
Horii A, Han HJ, Shimada M, Yanagisawa A, Kato Y, Ohta H, et al.
Frequent replication errors at microsatellite loci in tumors of patients with multiple primary cancers. Cancer Res 1994;54:3373-5.
Kimura K, Shinmura K, Hasegawa T, Beppu Y, Yokoyama R, Yokota J. Germline p53 mutation in a patient with multiple primary cancers. Jpn J Clin Oncol 2001;31:349-51.
Morris LG, Sikora AG, Hayes RB, Patel SG, Ganly I. Anatomic sites at elevated risk of second primary cancer after an index head and neck cancer. Cancer Causes Control 2011;22:671-9.
Jablon C. Epidemiologic perspectives in radiation carcinogenesis. In: Boice JD Jr., editors. Radiation Carcinogenesis: Epidemiology and Biological Significance. New York: Raven Press, International Agency; 1994. p. 1-8.
Gilbert ES, Stovall M, Gospodarowicz M, Van Leeuwen FE, Andersson M, Glimelius B, et al.
Lung cancer after treatment for Hodgkin's disease: Focus on radiation effects. Radiat Res 2003;159:161-73.
Rubino C, Shamsaldin A, Lê MG, Labbé M, Guinebretière JM, Chavaudra J, et al.
Radiation dose and risk of soft tissue and bone sarcoma after breast cancer treatment. Breast Cancer Res Treat 2005;89:277-88.
Travis LB, Gospodarowicz M, Curtis RE, Clarke EA, Andersson M, Glimelius B, et al.
Lung cancer following chemotherapy and radiotherapy for Hodgkin's disease. J Natl Cancer Inst 2002;94:182-92.
Hajdu SI, Hajdu EO. Multiple primary malignant tumors. J Am Geriatr Soc 1968;16:16-26.
Berge T, Cederqvist L, Schönebeck J. Multiple primary malignant tumours. An autopsy study of a circumscribed population. Acta Pathol Microbiol Scand 1969;76:171-83.
Aydiner A, Karadeniz A, Uygun K, Tas S, Tas F, Disci R, et al.
Multiple primary neoplasms at a single institution: Differences between synchronous and metachronous neoplasms. Am J Clin Oncol 2000;23:364-70.
Lee TK, Barringer M, Myers RT, Sterchi JM. Multiple primary carcinomas of the colon and associated extracolonic primary malignant tumors. Ann Surg 1982;195:501-7.
Vyas JJ, Deshpande RK, Sharma S, Desai PB. Multiple primary cancers in Indian population: Metachronous and synchronous lesions. J Surg Oncol 1983;23:239-49.
Lee TK, Myers RT, Scharyj M, Marshall RB. Multiple primary malignant tumors (MPMT): Study of 68 autopsy cases (1963-1980). J Am Geriatr Soc 1982;30:744-53.
Gursel B, Meydan D, Özbek N, Ozdemir O, Odabas E. Multiple primary malignant neoplasms from the black sea region of Turkey. J Int Med Res 2011;39:667-74.
Flannery JT, Boice JD Jr., Devesa SS, Kleinerman RA, Curtis RE, Fraumeni JF Jr. Cancer registration in Connecticut and the study of multiple primary cancers, 1935-1982. Natl Cancer Inst Monogr 1985;68:13-24.
Balat O, Kudelka AP, Ro JY, Edwards CL, Balbay D, Dinney C, et al.
Two synchronous primary tumors of the ovary and kidney: A case report. Eur J Gynaecol Oncol 1996;17:257-9.
Ozturk MA, Dane F, Kaygusuz I, Asmaz O, Uzay A, Bayik M, et al.
Synchronous renal cell carcinoma and multiple myeloma: Report of two cases and review of the literature. J BUON 2009;14:511-4.
Hayat MJ, Howlader N, Reichman ME, Edwards BK. Cancer statistics, trends, and multiple primary cancer analyses from the Surveillance, Epidemiology, and End Results (SEER) program. Oncologist 2007;12:20-37.
Engin K. Cancers in multiple primary sites. Int Surg 1994;79:33-7.
Vogel VG. Identifying and screening patients at risk of second cancers. Cancer Epidemiol Biomarkers Prev 2006;15:2027-32.
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3]
|This article has been cited by|
||Second primary malignancies in patients with radiotherapy-treated laryngeal carcinoma - A commentary
| ||Deepti Sharma,Neha Sharma,Vineeta Goel |
| ||Indian Journal of Cancer. 2019; 56(1): 35 |
|[Pubmed] | [DOI]|
||Multiple Primary Malignancies of Cancer of Ovary and Cervix in A Young Woman: A Rare Case Report
| ||Sangeeta Pankaj,Anjili Kumari,Syed Nazneen,Jaya Kumari,Vijayanand Choudhary,Anita Kmari |
| ||Indian Journal of Gynecologic Oncology. 2018; 16(2) |
|[Pubmed] | [DOI]|