The ris­ing cancer bur­den in Asia

The bur­den of cancer care world­wide is ex­pected to in­crease in the next decade and be­yond. With pop­u­la­tion growth, age­ing and risk fac­tors, the es­ti­mates by bod­ies such as the World Health Or­gan­i­sa­tion (WHO) sug­gest that cancer deaths will in­crease by 45

BioSpectrum (Asia) - - BIO CONTENT - Dr Robert Lim, Med­i­cal On­col­ogy Spe­cial­ist, Icon SOC Far­rer Park Med­i­cal Clinic, Sin­ga­pore

Although age­ing as a risk fac­tor can­not be al­tered, cer­tain lifestyle fac­tors and in­fec­tions are amenable to change with the po­ten­tial to im­pact on this ris­ing in­ci­dence. To­bacco use is the most im­por­tant risk fac­tor and in­fec­tions rang­ing from hep­ati­tis to hu­man pa­pil­loma virus (HPV) con­trib­ute sig­nif­i­cantly to this ris­ing epi­demic. It is wor­thy to note that vac­ci­na­tions are avail­able for hep­ati­tis B and HPV nowa­days. Al­co­hol con­sump­tion is an­other risk fac­tor and is com­monly as­so­ci­ated with life­styles that in­clude smok­ing. It is not un­com­mon that pa­tients present in the later stages of dis­ease and es­pe­cially in lower in­come coun­tries, ac­cess to di­ag­nos­tic ser­vices and care may be less avail­able. With Asia’s pop­u­la­tion poised to con­sti­tute about half of the world’s pop­u­la­tion, the im­pact of cancer in Asia will have ma­jor im­pli­ca­tions on the health and economies of the coun­tries af­fected. Types of cancer in males that are pre­dicted to pre­dom­i­nate would in­clude: lung, stom­ach, liver, col­orec­tal, oe­soph­a­gus, prostate and blad­der. In fe­males, these would in­clude: breast, cer­vi­cal, lung, stom­ach, col­orec­tal, liver and uter­ine.

For decades, treat­ment par­a­digms have been driven prin­ci­pally by re­search and data de­rived from Western pop­u­la­tions. How­ever, with the ris­ing aware­ness of the need to de­rive more Asian-cen­tric data, more ef­forts have been made by re­searchers and phar­ma­ceu­ti­cal com­pa­nies to in­vest in this facet of re­search. The much-quoted il­lus­tra­tion of how lung cancer types dif­fer be­tween Cau­casian pop­u­la­tions

and East Asians is a case in point. The de­vel­op­ment of drugs that tar­get the Epi­der­mal Growth Fac­tor Re­cep­tor (EGFR) in lung cancer did not see much ben­e­fit in a pre­dom­i­nantly Cau­casian pop­u­la­tion. It was the sub­se­quent find­ing of a higher in­ci­dence of non-smok­ing re­lated lung cancer in East Asians who were then found to have a higher preva­lence of EGFR mu­ta­tions, that cul­mi­nated in stud­ies that showed much more ben­e­fit for this spe­cific group of pa­tients who re­ceived this class of drug. The recog­ni­tion that lung cancer types vary sig­nif­i­cantly has led to fur­ther ex­plo­ration of var­i­ous driver mu­ta­tions for this cancer, with fur­ther suc­cess in iden­ti­fy­ing other sub­sets which now can ben­e­fit from spe­cific tar­geted drugs.

Re­search into is­sues per­tain­ing to drug me­tab­o­lism and in par­tic­u­lar the dif­fer­ences be­tween Western pop­u­la­tions and Asians has also led to a bet­ter un­der­stand­ing of the ra­tio­nale for rec­om­mend­ing dif­fer­ent doses and sched­ules for pa­tients. Ex­am­ples range from higher tox­i­c­i­ties from lower clear­ance of Do­c­etaxel in East Asians to bet­ter tol­er­ance of oral Capecitabine in East Asians as com­pared with Cau­casians. Hence, the old par­a­digm of de­ter­min­ing treat­ment guide­lines solely based on Western hemi­sphere de­rived data is grad­u­ally shift­ing, with greater aware­ness of the need to con­duct well-planned stud­ies in Asian pop­u­la­tions.

Not­with­stand­ing the dif­fer­ences be­tween eth­nic­i­ties, many of the key clin­i­cal tri­als that have been con­ducted in the in­ter­na­tional arena have helped shape the ex­cit­ing break­throughs in cancer ther­apy. In­clu­sion of many Asian cen­tres in these stud­ies have helped en­sure con­fi­dence in the find­ings that can there­fore be ap­plied lo­cally. Over­all, the in­vest­ment in sci­ence is reap­ing div­i­dends with pa­tients ben­e­fit­ing. From an im­prove­ment in un­der­stand­ing cell cy­cle ki­net­ics, to ap­pre­ci­at­ing how blood ves­sel growth is an es­sen­tial part of a ma­lig­nant tu­mour’s growth, to iden­ti­fy­ing onco­genic driver mu­ta­tions that are the main growth im­pe­tus in se­lect can­cers and to un­lock­ing in­hibitory sig­nals on im­mune cells, these ex­am­ples of “bench” work have now given rise to ac­tual ther­a­peu­tic mol­e­cules and drugs lit­er­ally and fig­u­ra­tively at the “bed­side”. Head­lines in the me­dia have her­alded a newer age of ther­a­peu­tics whereby mul­ti­ple facets of cancer growth can be tar­geted be­yond the tra­di­tional chemo­ther­apy drugs. Hence the coin­ing of “tar­geted ther­apy” has been an apt de­scrip­tion of these newer novel ther­a­pies.

Op­tions for treat­ment would also in­clude surgery and ra­di­a­tion ther­apy, with the former a key con­sid­er­a­tion for the aims of cu­ra­tive treat­ment in early stage cancer. We have also seen ad­vances in these dis­ci­plines that fre­quently com­bine sci­ence with engi­neer­ing in­ge­nu­ity. La­paro­scopic (“key­hole”) surgery is now a main­stay for many stan­dard pro­ce­dures, with equiv­a­lent re­sults but less mor­bid­ity and quicker re­cov­ery as com­pared with tra­di­tional “open” surgery. The clas­sic sight of a sur­geon pos­tured over a pa­tient has changed to one where there is ma­nip­u­la­tion of in­stru­ments from out­side the pa­tient’s body, guided by the im­ages on a video

screen.

Ro­botic surgery where the sur­geon sits and utilises the unique agility of me­chan­i­cal arms es­pe­cially in nar­row or con­fined re­gions of the body, can al­low for less trau­matic re­sec­tions of tu­mours. Ra­dio­ther­apy op­tions have also pro­gressed with greater pre­ci­sion and the abil­ity to plan treat­ments to con­form to the shape and vol­ume of can­cers, which of­ten grow in asym­met­ri­cal ways to give rise to dif­fer­ent shapes. Such fo­cussed ther­apy has helped not just de­liver more pre­cise doses but also min­imises ef­fects to sur­round­ing tis­sue. Com­puter sys­tems and soft­ware are now also able to co­or­di­nate the tim­ing of ra­di­a­tion in ac­cor­dance to a pa­tient’s breath­ing to also fur­ther min­imise doses to nor­mal tis­sue.

The abil­ity to un­der­stand the na­ture and ex­tent of a cancer issue is of great im­por­tance in de­ter­min­ing the most ap­pro­pri­ate treat­ment plan. Di­ag­nos­tic and imag­ing stud­ies have a role which can­not be un­der­stated. Just as with how in­no­va­tion has led to im­proved treat­ments, we have also seen how newer scan­ning tech­nolo­gies and more ac­cu­rate di­ag­nos­tic ca­pa­bil­i­ties greatly ben­e­fit pa­tients and fam­i­lies. The tra­di­tional man­ner of per­form­ing a biopsy of the prostate by the urol­o­gist may give way to a more pre­cise MRI guided ap­proach as re­cently demon­strated. And to aid the pathol­o­gist in de­ter­min­ing the di­ag­no­sis and type of ma­lig­nant cell, tech­niques range from sim­ple stains to ge­netic analy­ses. Prog­nos­tic and pre­dic­tive tests and pan­els are of­ten con­sid­ered to help in treat­ment de­ci­sions and the ad­vent of ex­ome se­quenc­ing on multi-gene pan­els to search for an ar­ray of ge­netic mu­ta­tions has al­tered the ap­proach for di­ag­no­sis and treat­ment se­lec­tion.

How­ever, much as the ar­ma­men­tar­ium for treat­ment has greatly im­proved, cer­tain chal­lenges re­main for Asian coun­tries. The wide vari­ance in de­vel­op­ment of each coun­try or re­gion, cou­pled with dif­fer­ing eco­nomic strengths, gov­er­nance and health­care ca­pa­bil­i­ties means that there re­mains an im­mense dif­fer­ence in ac­cess to di­ag­no­sis and care for pa­tients. Each health­care sys­tem is mod­elled dif­fer­ently with dif­fer­ent payment or re­im­burse­ment sys­tems, and the het­ero­gene­ity of pop­u­la­tions makes for vary­ing risks of types of cancer and their pre­sen­ta­tions.

Screen­ing pro­grammes to de­tect pre-ma­lig­nant changes or early stage cancer have re­ceived in­ad­e­quate at­ten­tion and fo­cus at na­tional lev­els for most coun­tries. A re­sound­ing con­cern of late has been the ques­tion of man­ag­ing health­care costs, which has seen ex­pen­di­ture from gov­ern­ments, third party pay­ers and pa­tients rise sig­nif­i­cantly.

In Sin­ga­pore, the Agency for Care Ef­fec­tive­ness (ACE) has been es­tab­lished by the Min­istry of Health to help drive clin­i­cally ef­fec­tive and cost-ef­fec­tive pa­tient care, fol­low­ing the lead of other coun­tries such as the United King­dom’s Na­tional In­sti­tute for Health and Care Ex­cel­lence (NICE). All these chal­lenges should not be in­sur­mount­able, but will pose ob­sta­cles to pro­vid­ing eq­ui­table, state-of-the-art yet cost-ef­fec­tive cancer care for Asians.

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