Second primary cancer in head and neck cancer patients

1. Second primary cancer in head and neck cancer patients Cristina Bosetti Department of Epidemiology, Istituto di Ricerche Farmacologiche "Mario Negri" Milan, Italy January 27, 2012

2. Second primary cancer in head and neck cancer patients Patients who had a cancer of the head and neck (HN) have a substantial excess risk of a second primary cancer (SPC), and this is a major reason for their poor prognosis.

3. Second primary cancer in head and neck cancer patients We investigated the risk of SPC following a primary HN cancer (i.e., oral cavity, pharynx, and larynx) on the basis of data from 13 population-based cancer registries from Europe, Canada, Australia and Singapore for the years 1943–2000. Bosetti et al. Int J Cancer 2011; 129:173-179.

4. Second primary cancer in head and neck cancer patients • A total of 99,257 patients had a first primary HN cancer • 15,985 tongue • 22,378 mouth • 20,758 pharynx • 40,190 larynx • contributing to 489,855 person-years of follow-up (mean follow-up 4.9 yrs) • mean follow-up 4.9 yrs • contributing to 489,855 person-years

5. Standardized incidence ratios (SIR) To assess the excess risk of SPCs in the cohort as compared to the general population we computed the standardized incidence ratios (SIR) SIR=Observed numbers of SPCs/Expected number of cancers (x 100) calculated from accumulated person-years and the age-, sex- and calendar period-specific first primary cancer incidence rates in each cancer registry

6. Second primary cancer in head and neck cancer patients A total of 10,826 patients was diagnosed with a SPC, SIR 1.86 (95% CI = 1.83–1.90).

7. Second primary cancer in head and neck cancer patients A total of 10,826 patients was diagnosed with a SPC, SIR 1.86 (95% CI = 1.83–1.90). 1,294 had a SPC at the HN versus 115.75 expected, SIR=11.2 (95% CI 10.6-11.8).

8. Number and SIR of SPC in HN cancer patients

9. Second primary cancer in head and neck cancer patients These patterns are consistent with the notion that the pattern of cancer in survivors of HN cancer is dominated by the effect of tobacco smoking and alcohol drinking.

10. SPC at the HN by age at diagnosis of first HN cancer

11. SPC at the HN by sex and age at diagnosis of first HN cancer

12. Incidence of SPC at the HN and its pattern with age Limited data are available on the age-relation of incidence of SPC at the NH Sex- and age-specific Incidence rates (x100,000)= =N. new cases/population at risk in each sex and age group (1 year)

13. Age-specific incidence rate of first HN cancer

14. Second primary cancer in head and neck cancer patients Male incidence rates of first HN cancer steeply increased with age, from 0.68/100,000 at age 30–34 to 46.2/100,000 at age 70–74, and leveled off at older age; female incidence increased from 0.50/100,000 at age 30–34 to 16.5/100,000 at age 80–84.

15. Age-specific incidence rate of SPC at HN after a first HN cancer - Male

16. Age-specific incidence rate of SPC at HN after a first HN cancer - Female

17. Age-specific incidence rate of SPC at HN after a first HN cancer Age-specific incidence of SPC at the HN after a first HN cancer in men was around 200–300/100,000 between age 40–44 and age 70–74 and tended to decline at subsequent ages (150/100,000 at age 80–84); in women, incidence of second HN cancers was around 200–300/100,000 between age 45–49 and 80–84.

18. Age-specific incidence rate of SPC at HN after a first HN cancer - Male

19. Age-specific incidence rate of SPC at HN after a first HN cancer - Female

20. Cancer Registry of the Swiss Canton of Vaud – Age-specific incidence of SPC Breast-Invasive Breast-In situ Oral cavity/pharynx Colorectum Levi et al. Eur J Cancer Prev 17:385-388

21. The power relation with age of the incidence of first primary HN cancer has been interpreted within the multistage model of carcinogenesis (Armitage and Doll, 1961). Armitage P, Doll R. A two-stage theory of carcinogenesis in relation to the age distribution of human cancer. Br J Cancer 1961;11:161–9. Age-specific incidence rate of SPC at HN after a first HN cancer

22. The constant age patterns of SPC at HN indicate that this population of susceptible individuals may need a single additional mutational event to develop a second cancer (Peto and Mack 2000). Peto J, Mack TM. High constant incidence in twins and other relatives of women with breast cancer. Nat Genet 2000;26:411–4. Age-specific incidence rate of SPC at HN after a first HN cancer

23. Subjectswith a primarycancer of the HN differ from the general population in several aspects: SPC at HN after a first HN cancer

24. Subjectswith a primarycancer of the HN differ from the general population in several aspects: Particularly cancer susceptible subjects. SPC at HN after a first HN cancer

25. Subjectswith a primarycancer of the HN differ from the general population in several aspects: Particularly cancer susceptible subjects. The exposure to the agents which caused the primary tumors may also have triggered the development of multiple primary cancers at other HN sites. SPC at HN after a first HN cancer

26. Subjectswith a primarycancer of the HN differ from the general population in several aspects: Particularly cancer susceptible subjects. The exposure to the agents which caused the primary tumors may also have triggered the development of multiple primary cancers at other HN sites. The treatments for their first cancer may also affect their risk of developing a subsequentprimarycancer. SPC at HN after a first HN cancer

27. Patients with a primary cancer at the HN have a substantial excess risk of SPCs at the HN as compared to the general population. Conclusion (1)

28. The incidence of second HN cancers does not increase with age, but remains constant, or if anything, decreases with advancing age. Conclusion (2)

29. The incidence of second HN cancers does not increase with age, but remains constant, or if anything, decreases with advancing age. to selective stopping of risk factors modifiable in middle and elderly age progressive elimination of predisposed (very high risk) individuals at young ages Conclusion (2)

30. In terms of individual risk assessment and clinical implications, these results indicate that young HN cancer patients, although rare, are at particularly high risk of developing another primary cancer in the HN. The rates of second HN cancers of the order of 150 to 250/100,000 in the fifth decade of age are indeed comparable or larger than the rates of all cancers in the general population at age 40 to 49. Conclusion (3)

31. Thank you for your attention!

32. Second primary cancer in head and neck cancer patients A total of 99,257 patients had a first primary HN cancer (15,985 tongue, 22,378 mouth, 20,758 pharyngeal, and 40,190 laryngeal cancer), contributing to 489,855 person-years of follow-up (mean follow-up 4.9 yrs).

33. Age-specific incidence rate of first HN cancer - Male

34. Age-specific incidence rate of first HN cancer - Male

35. Age-specific incidence rate of first HN cancer - Male

36. Age-specific incidence rate of first HN cancer - Female

37. Second primary cancer in head and neck cancer patients Male incidence rates of first HN cancer steeply increased with age, from 0.68/100,000 at age 30–34 to 46.2/100,000 at age 70–74, and leveled off at older age; female incidence increased from 0.50/100,000 at age 30–34 to 16.5/100,000 at age 80–84.

38. Age-specific incidence rate of SPC at HN after a first HN cancer Age-specific incidence of SPC at the HN after a first HN cancer in men was around 200–300/100,000 between age 40–44 and age 70–74 and tended to decline at subsequent ages (150/100,000 at age 80–84); in women, incidence of second HN cancers was around 200–300/100,000 between age 45–49 and 80–84.