- Email: [email protected]
Cancer transition and priorities for cancer control
Comment
to inhibit the MAPK pathway in tumours, to improve clinical responses. Successful targeting of RAS-induced transformation is a major goal of cancer drug development. Falchook, Infante, and colleagues did note some activity of trametinib in RAS-mutant cancers.8,9 Could MEK inhibitors be combined with other agents to enhance pathway inhibition in RAS-mutant cancers? The RAS oncogenes and others that activate the MAPK pathway are now firmly in our sights. Grant A McArthur Division of Cancer Medicine and Research, Peter MacCallum Cancer Centre, East Melbourne, VIC 8006, Australia [email protected]
3 4 5
6
7
8
9
10 I have received research support from Pfizer, Millennium, and Novartis. 1 2
Solit DB, Garraway LA, Pratilas CA, et al. BRAF mutation predicts sensitivity to MEK inhibition. Nature 2006; 439: 358–62. Drosten M, Dhawahir A, Sum EY, et al. Genetic analysis of Ras signalling pathways in cell proliferation, migration and survival. EMBO J 2010; 29: 1091–104.
11
Malumbres M, Barbacid M. RAS oncogenes: the first 30 years. Nat Rev Cancer 2003; 3: 459–65. Flaherty KT, Puzanov I, Kim KB, et al. Inhibition of mutated, activated BRAF in metastatic melanoma. N Engl J Med 2010; 363: 809–19. Falchook GS, Long GV, Kurzrock R, et al. Dabrafenib in patients with melanoma, untreated brain metastases, and other solid tumours: a phase 1 dose-escalation trial. Lancet 2012; 379: 1893–901. Heidorn SJ, Milagre C, Whittaker S, et al. Kinase-dead BRAF and oncogenic RAS cooperate to drive tumor progression through CRAF. Cell 2010; 140: 209–21. Gilmartin AG, Bleam MR, Groy A, et al. GSK1120212 (JTP-74057) is an inhibitor of MEK activity and activation with favorable pharmacokinetic properties for sustained in vivo pathway inhibition. Clin Cancer Res 2011; 17: 989–1000. Infante JR, Fecher LA, Falchook GS, et al. Safety, pharmacokinetic, pharmacodynamic, and efficacy data for the oral MEK inhibitor trametinib: a phase 1 dose-escalation trial. Lancet Oncol 2012; published online July 16. http://dx.doi.org/10.1016/S1470-2045(12)70270-X. Falchook GS, Lewis KD, Infante JR, et al. Activity of the oral MEK inhibitor trametinib in patients with advanced melanoma: a phase 1 doseescalation trial. Lancet Oncol 2012; published online July 16. http://dx. doi.org/10.1016/S1470-2045(12)70269-3. Flaherty KT, Robert C, Hersey P, et al, for the METRIC Study Group. Improved survival with MEK inhibition in BRAF-mutated melanoma. N Engl J Med 2012 published online June 4. DOI:10.1056/ NEJMoa1203421. Sosman JA, Kim KB, Schuchter L, et al. Survival in BRAF V600-mutant advanced melanoma treated with vemurafenib. N Engl J Med 2012; 366: 707–14.
Cancer transition and priorities for cancer control In The Lancet Oncology, Freddie Bray and colleagues1 assess worldwide patterns of cancer burden, in terms of both incidence and mortality, and predict future scenarios in relation to different levels of socioeconomic development, which they measure using the Human Development Index (HDI). Their paper, which provides a good explanation of the theory of cancer transition, serves both purposes of research and guidance in setting priorities for cancer control. Cancer transition can be regarded as an extension or completion of Omran’s theory on epidemiological transition.2,3 In analogy with the third stage of epidemiological transition—a shift from infectious to non-communicable diseases—the theory of cancer transition sees a shift from a predominance of cancers linked to infections to cancers associated with risk factors that are mainly non-infectious and possibly related to a so-called western lifestyle. So, whereas in very high and high HDI areas four cancer types (lung, female breast, colorectum, and prostate) account for almost half the total cancer incidence burden, in middle and low HDI areas, in addition to cancers of the lung, colorectum, and female breast, cancers of www.thelancet.com/oncology Vol 13 August 2012
the stomach, liver, and cervix account for a substantial burden of cancer.1 In areas with low HDI, the most frequent cancer types seem to be those of the cervix, female breast, liver, Kaposi's sarcoma, and nonHodgkin lymphoma.1 Bray and colleagues’ findings1 show that, in 2008, the largest cancer burden was in very high HDI areas, which bore almost 40% of the global incidence burden despite accounting for only 15% of the world’s population; low HDI areas bore only 2% of the burden, with a population accounting for nearly 6% of the global population. However, Bray and colleagues’ projections for 2030 predict the largest absolute increase in low HDI areas. And the proportion of the global burden of cancer borne in low HDI areas might be higher if only the population older than 50 years are considered—people in this age group are most susceptible to cancer and are likely to account for a smaller proportion of the national population in low HDI countries. Furthermore, with respect to projected burdens, the socioeconomic level in low HDI countries is expected to improve (as implicit in the demographic projections that assume decreasing population growth), which will in turn increase the incidence of
See Articles page 790
745
Comment
cancer because of both population ageing and the spread of new risk factors. For these reasons, cancer burden in lower HDI areas will probably become a more serious problem in the future than it seems now. The analysis of cancer burden and trends together with future projections shows where different populations stand along the epidemic curve and might help to identify the most useful interventions. The knowledge gained in areas where more advanced stages of cancer transition have been reached is crucial to guide implementation of preventive action in those that still lag behind. In the theory of epidemiological transition,3 the shift from infections to degenerative diseases in Europe was not associated with progress in medical science but rather with improved socioeconomic conditions (that in turn improved nutrition and hygiene).4 Medical progress became more important at a later stage in high-income countries, but was seen to have a great effect in low-income countries, causing accelerated epidemiological transitions. Should the analogy with Omran’s theory hold, implementation of preventive measures to eradicate known risk factors in low and middle HDI countries could be most effective and could change the shape of the cancer epidemiological curve for most of the world’s population (more than 70% putting together middle and low HDI countries). Public health programmes should include campaigns for immunisation,5 tobacco control, reduction in alcohol consumption and obesity,6 and the implementation of cancer-screening programmes that have been shown to reduce mortality effectively.7 In very high HDI areas, there is strong evidence of the simultaneous start of decline of lung cancer incidence,8 at least in men, and the rise and increasing
relative importance of other cancer types (eg, kidney, pancreas,8 testis9), often with unknown cause or known risk factors that explain only a small fraction of cases. In such areas, which are at the front edge of the cancer epidemic curve, has cancer transition theory been fully realised or has a new epidemic stage—a shift to other cancer types related to risk factors that are still unknown—become apparent? The answer and the possible strategies to counteract the rise of new diseases depend entirely on our ability to understand the patterns of their emergence and identify their causes. Milena Maule, *Franco Merletti University of Turin, Department of Medical Sciences, Cancer Epidemiology Unit, CeRMS and CPO-Piemonte, Turin 10126, Italy [email protected] We declare that we have no conflicts of interest. 1
2 3 4 5
6 7
8
9
Bray F, Jemal A, Grey N, Ferlay J, Forman D. Global cancer transitions according to the Human Development Index (2008–2030): a population-based study. Lancet Oncol 2012; 13: 790–801. Gersten O, Wilmoth JR. The cancer transition in Japan since 1951. Demographic Research 2002; 7: 271–306. Omran AR. The epidemiologic transition. A theory of the epidemiology of population change. Milbank Mem Fund Q 1971; 49: 509–38. McKeown T, Brown RG. Medical evidence related to English population change in the eighteenth century. Population Studies 1955; 9: 119–41. Sylla BS, Wild CP. A million africans a year dying from cancer by 2030: what can cancer research and control offer to the continent? Int J Cancer 2011; 130: 245–50. Beaglehole R, Bonita R, Horton R, et al. Priority actions for the non-communicable disease crisis. Lancet 2011; 377: 1438–47. Peto J, Gilham C, Fletcher O, Matthews FE. The cervical cancer epidemic that screening has prevented in the UK. Lancet 2004; 364: 249–56. Kohler BA, Ward E, McCarthy BJ, et al. Annual report to the nation on the status of cancer, 1975–2007, featuring tumors of the brain and other nervous system. J Natl Cancer Inst 2011; 103: 714–36. Chia VM, Quraishi SM, Devesa SS, Purdue MP, Cook MB, McGlynn KA. International trends in the incidence of testicular cancer, 1973–2002. Cancer Epidemiol Biomarkers Prev 2010; 19: 1151–59.
Stereotactic ablative radiotherapy for inoperable stage I NSCLC Published Online June 22, 2012 http://dx.doi.org/10.1016/ S1470-2045(12)70282-6 See Articles page 802
746
Over the past 10 years, stereotactic ablative radiotherapy (SABR) has emerged as a viable treatment option for inoperable stage I non-smallcell lung cancer (NSCLC). In prospective and large retrospective studies in patients with considerable comorbidity and limited curative treatment options,1–5 high local control has been reported, reaching nearly 95% at 3 years with low toxicity. So far, SABR has been
the most cost-effective treatment compared with radiofrequency ablation or conventional radiotherapy in inoperable stage I lung cancer.6 Therefore, sensible use of SABR and scientific assessment of advances in radiation therapy and accompanying technology are warranted to truly acknowledge its benefits. Although encouraging and published in high-ranked journals, most reported series have had limited patient www.thelancet.com/oncology Vol 13 August 2012
to inhibit the MAPK pathway in tumours, to improve clinical responses. Successful targeting of RAS-induced transformation is a major goal of cancer drug development. Falchook, Infante, and colleagues did note some activity of trametinib in RAS-mutant cancers.8,9 Could MEK inhibitors be combined with other agents to enhance pathway inhibition in RAS-mutant cancers? The RAS oncogenes and others that activate the MAPK pathway are now firmly in our sights. Grant A McArthur Division of Cancer Medicine and Research, Peter MacCallum Cancer Centre, East Melbourne, VIC 8006, Australia [email protected]
3 4 5
6
7
8
9
10 I have received research support from Pfizer, Millennium, and Novartis. 1 2
Solit DB, Garraway LA, Pratilas CA, et al. BRAF mutation predicts sensitivity to MEK inhibition. Nature 2006; 439: 358–62. Drosten M, Dhawahir A, Sum EY, et al. Genetic analysis of Ras signalling pathways in cell proliferation, migration and survival. EMBO J 2010; 29: 1091–104.
11
Malumbres M, Barbacid M. RAS oncogenes: the first 30 years. Nat Rev Cancer 2003; 3: 459–65. Flaherty KT, Puzanov I, Kim KB, et al. Inhibition of mutated, activated BRAF in metastatic melanoma. N Engl J Med 2010; 363: 809–19. Falchook GS, Long GV, Kurzrock R, et al. Dabrafenib in patients with melanoma, untreated brain metastases, and other solid tumours: a phase 1 dose-escalation trial. Lancet 2012; 379: 1893–901. Heidorn SJ, Milagre C, Whittaker S, et al. Kinase-dead BRAF and oncogenic RAS cooperate to drive tumor progression through CRAF. Cell 2010; 140: 209–21. Gilmartin AG, Bleam MR, Groy A, et al. GSK1120212 (JTP-74057) is an inhibitor of MEK activity and activation with favorable pharmacokinetic properties for sustained in vivo pathway inhibition. Clin Cancer Res 2011; 17: 989–1000. Infante JR, Fecher LA, Falchook GS, et al. Safety, pharmacokinetic, pharmacodynamic, and efficacy data for the oral MEK inhibitor trametinib: a phase 1 dose-escalation trial. Lancet Oncol 2012; published online July 16. http://dx.doi.org/10.1016/S1470-2045(12)70270-X. Falchook GS, Lewis KD, Infante JR, et al. Activity of the oral MEK inhibitor trametinib in patients with advanced melanoma: a phase 1 doseescalation trial. Lancet Oncol 2012; published online July 16. http://dx. doi.org/10.1016/S1470-2045(12)70269-3. Flaherty KT, Robert C, Hersey P, et al, for the METRIC Study Group. Improved survival with MEK inhibition in BRAF-mutated melanoma. N Engl J Med 2012 published online June 4. DOI:10.1056/ NEJMoa1203421. Sosman JA, Kim KB, Schuchter L, et al. Survival in BRAF V600-mutant advanced melanoma treated with vemurafenib. N Engl J Med 2012; 366: 707–14.
Cancer transition and priorities for cancer control In The Lancet Oncology, Freddie Bray and colleagues1 assess worldwide patterns of cancer burden, in terms of both incidence and mortality, and predict future scenarios in relation to different levels of socioeconomic development, which they measure using the Human Development Index (HDI). Their paper, which provides a good explanation of the theory of cancer transition, serves both purposes of research and guidance in setting priorities for cancer control. Cancer transition can be regarded as an extension or completion of Omran’s theory on epidemiological transition.2,3 In analogy with the third stage of epidemiological transition—a shift from infectious to non-communicable diseases—the theory of cancer transition sees a shift from a predominance of cancers linked to infections to cancers associated with risk factors that are mainly non-infectious and possibly related to a so-called western lifestyle. So, whereas in very high and high HDI areas four cancer types (lung, female breast, colorectum, and prostate) account for almost half the total cancer incidence burden, in middle and low HDI areas, in addition to cancers of the lung, colorectum, and female breast, cancers of www.thelancet.com/oncology Vol 13 August 2012
the stomach, liver, and cervix account for a substantial burden of cancer.1 In areas with low HDI, the most frequent cancer types seem to be those of the cervix, female breast, liver, Kaposi's sarcoma, and nonHodgkin lymphoma.1 Bray and colleagues’ findings1 show that, in 2008, the largest cancer burden was in very high HDI areas, which bore almost 40% of the global incidence burden despite accounting for only 15% of the world’s population; low HDI areas bore only 2% of the burden, with a population accounting for nearly 6% of the global population. However, Bray and colleagues’ projections for 2030 predict the largest absolute increase in low HDI areas. And the proportion of the global burden of cancer borne in low HDI areas might be higher if only the population older than 50 years are considered—people in this age group are most susceptible to cancer and are likely to account for a smaller proportion of the national population in low HDI countries. Furthermore, with respect to projected burdens, the socioeconomic level in low HDI countries is expected to improve (as implicit in the demographic projections that assume decreasing population growth), which will in turn increase the incidence of
See Articles page 790
745
Comment
cancer because of both population ageing and the spread of new risk factors. For these reasons, cancer burden in lower HDI areas will probably become a more serious problem in the future than it seems now. The analysis of cancer burden and trends together with future projections shows where different populations stand along the epidemic curve and might help to identify the most useful interventions. The knowledge gained in areas where more advanced stages of cancer transition have been reached is crucial to guide implementation of preventive action in those that still lag behind. In the theory of epidemiological transition,3 the shift from infections to degenerative diseases in Europe was not associated with progress in medical science but rather with improved socioeconomic conditions (that in turn improved nutrition and hygiene).4 Medical progress became more important at a later stage in high-income countries, but was seen to have a great effect in low-income countries, causing accelerated epidemiological transitions. Should the analogy with Omran’s theory hold, implementation of preventive measures to eradicate known risk factors in low and middle HDI countries could be most effective and could change the shape of the cancer epidemiological curve for most of the world’s population (more than 70% putting together middle and low HDI countries). Public health programmes should include campaigns for immunisation,5 tobacco control, reduction in alcohol consumption and obesity,6 and the implementation of cancer-screening programmes that have been shown to reduce mortality effectively.7 In very high HDI areas, there is strong evidence of the simultaneous start of decline of lung cancer incidence,8 at least in men, and the rise and increasing
relative importance of other cancer types (eg, kidney, pancreas,8 testis9), often with unknown cause or known risk factors that explain only a small fraction of cases. In such areas, which are at the front edge of the cancer epidemic curve, has cancer transition theory been fully realised or has a new epidemic stage—a shift to other cancer types related to risk factors that are still unknown—become apparent? The answer and the possible strategies to counteract the rise of new diseases depend entirely on our ability to understand the patterns of their emergence and identify their causes. Milena Maule, *Franco Merletti University of Turin, Department of Medical Sciences, Cancer Epidemiology Unit, CeRMS and CPO-Piemonte, Turin 10126, Italy [email protected] We declare that we have no conflicts of interest. 1
2 3 4 5
6 7
8
9
Bray F, Jemal A, Grey N, Ferlay J, Forman D. Global cancer transitions according to the Human Development Index (2008–2030): a population-based study. Lancet Oncol 2012; 13: 790–801. Gersten O, Wilmoth JR. The cancer transition in Japan since 1951. Demographic Research 2002; 7: 271–306. Omran AR. The epidemiologic transition. A theory of the epidemiology of population change. Milbank Mem Fund Q 1971; 49: 509–38. McKeown T, Brown RG. Medical evidence related to English population change in the eighteenth century. Population Studies 1955; 9: 119–41. Sylla BS, Wild CP. A million africans a year dying from cancer by 2030: what can cancer research and control offer to the continent? Int J Cancer 2011; 130: 245–50. Beaglehole R, Bonita R, Horton R, et al. Priority actions for the non-communicable disease crisis. Lancet 2011; 377: 1438–47. Peto J, Gilham C, Fletcher O, Matthews FE. The cervical cancer epidemic that screening has prevented in the UK. Lancet 2004; 364: 249–56. Kohler BA, Ward E, McCarthy BJ, et al. Annual report to the nation on the status of cancer, 1975–2007, featuring tumors of the brain and other nervous system. J Natl Cancer Inst 2011; 103: 714–36. Chia VM, Quraishi SM, Devesa SS, Purdue MP, Cook MB, McGlynn KA. International trends in the incidence of testicular cancer, 1973–2002. Cancer Epidemiol Biomarkers Prev 2010; 19: 1151–59.
Stereotactic ablative radiotherapy for inoperable stage I NSCLC Published Online June 22, 2012 http://dx.doi.org/10.1016/ S1470-2045(12)70282-6 See Articles page 802
746
Over the past 10 years, stereotactic ablative radiotherapy (SABR) has emerged as a viable treatment option for inoperable stage I non-smallcell lung cancer (NSCLC). In prospective and large retrospective studies in patients with considerable comorbidity and limited curative treatment options,1–5 high local control has been reported, reaching nearly 95% at 3 years with low toxicity. So far, SABR has been
the most cost-effective treatment compared with radiofrequency ablation or conventional radiotherapy in inoperable stage I lung cancer.6 Therefore, sensible use of SABR and scientific assessment of advances in radiation therapy and accompanying technology are warranted to truly acknowledge its benefits. Although encouraging and published in high-ranked journals, most reported series have had limited patient www.thelancet.com/oncology Vol 13 August 2012