Artificial Intelligence in Cancer: Diagnostic to Tailored Treatment

300 Pages·2020·10.909 MB·English

by  Smaranda Belciug

ARTIFICIAL INTELLIGENCE IN CANCER:
DIAGNOSTIC TO TAILORED TREATMENT
ARTIFICIAL
INTELLIGENCE
IN CANCER:
DIAGNOSTIC TO
TAILORED
TREATMENT
S B
MARANDA ELCIUG
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Dedication
In loving memory of myfather,Florin Gorunescu
If you remember me, then Idon’t care if everyone elseforgets
Haruki Murakami—Kafka on the Shore
Iwillalways rememberyou, Dad!
Foreword
This is an exceptional book. It takes the scientist learn about the human journey
reader through the cancer journey of a pa- and the real potential of relevant technical
tient, explaining at each stage what exactly methods to alleviate suffering.
it means for the patient and where artificial Assuchthebookisstructuredthroughthe
intelligence (AI) can and is helping all stages of the cancer patient journey starting
concernedtounderstandwhatishappening with the initial presentation of symptoms
andamelioratethejourneyandthepath.As anddiagnosisthroughpathologyandtesting
such it provides a very readable, yet techni- totreatment,involvingtheroleofAIinsur-
cal, description of the whole area of AI for gery,oncologyusingBigDataanddosecon-
thecancerpatientjourneythatcanbeunder- trol in radiology. This is followed by an
stood and enjoyed by students and re- explanation of survival analysis, including
searchers from many areas of computer lots of examples and case studies, so that
science, mathematics, statistics, physics, the reader can better calculate and compute
and related disciplines. Overall this is book future likelihood of remission, recurrence,
which combines passion and emotion with andlife-expectancyofthepatient,following
a comprehensive treatment of the whole their diagnosis and treatment. In the final
area, providing a very scholarly approach chapter the future of cancer research is
while communicating the basic ideas in a discussed,includingtheroleofAIinpallia-
clearandunderstandablemanner.Through- tive care.
outtherearelotsofexamples,web-linksand Overallthisisanoutstandingbookwhich
illustrations that makeit easyfor thenovice grasps its topic with enthusiasm and com-
or lay-person to appreciate the concepts, passionwhileshowcasingthebreadth,depth
while the more experienced reader can em- andapplicabilityofAIintreatingthecancer
pathize with the patient, their family and patient, as well as inspiring and motivating
the healthcare professionals while enjoying thereadertolearnmoreabouttheseexciting
thebackgroundanecdotes,instancesandex- new developments and possibilities.
planations. Thus, the patient can learn to
understand what is happening and how to SallyMcClean
interpret the evidence while the student or Portrush, Northern Ireland
ix
Preface
Dear reader, by continuing reading this thepatientsurvive?Wecomputethemwith
book you agree on embarking on a roller- survival analysis. When the miracle phrase:
coaster ride that will take you through the “you are in remission” is said, we jump up
ups and downs of Artificial Intelligence ap- anddownwithjoy.Butalsowefindoutthat
pliedincancerresearch.Youwillpassevery thenext5yearsarecrucial.Thewordrecur-
single stage that is lived by a cancer patient: rencehitsusrightinthechest.Whatarethe
findingoutthatshe/heissuspectedofhaving chances that the cancer will come back?
the disease, followed by all the tests, blood ArtificialIntelligenceisheretohelpuscom-
work and imaging, etc. The world collapses. putetheodds.Lastbutnotleast,inthefinal
But wait, a sparkle, a little light appears at chapter, we learn what might come next in
theendofthetunnel.Whatisthat?Itishope cancer research and how Artificial Intelli-
intheshapeofArtificialIntelligence. gence hasstarted to enter thepalliative care
Step by step, we see how the doctor’s also.WhetherArtificialIntelligencecanhelp
suspicion rises, and how the diagnostic is our dreams become true or not, only time
set using Artificial Intelligence. After that can tell.
we go into the pathology lab and watch the Thisbookisaddressedtocomputerscien-
pathologistatwork.WelearnhowArtificial tists, physicians, mathematicians, and the
Intelligenceisappliedinhistology,immuno- general public. I decided to write it in a
histochemistry, and genetics. One step fur- friendly way, so that you will want to keep
ther and we find ourselves in the operating on reading it. I wanted you to understand
room seeing the surgeon resecting tumors, that Artificial Intelligence is not voodoo,
after she/he preplanned the operation, notmagic,norsnakeoil.Itismathandsuper
learning everything about the tumor using computational power. In some parts of can-
Artificial Intelligence. The surgery is over, cer research, Artificial Intelligence is just in
the patient lives, and now she/he is about thebeginning.Ihopethatinthefuture doc-
tomeettherestoftheoncologyteam.Using torsanddatascientistswillcontinuetowork
BigData,ArtificialIntelligencehelpstheon- togetherindiscoveringnewwaysoffighting
cologist establish a tailored treatment plan, this awful disease.
taking into account everything she/he Thisbookisdedicatedtomyfather,Prof.
knows about the patient, from genetic data Florin Gorunescu, whom I lost in 2018 to a
toher/hiswayofliving. Maybechemother- rare aggressive form of esophageal cancer.
apyisnottheonlyanswer,maybeweneedto So, when I wrote every chapter I had him
follow the radiotherapist, and seehow she/ in mind and in my thoughts, and I relived
he can determine the right radiation dosage everything. That is why you may feel my
with the aid of Artificial Intelligence. emotions floating around in the pages of
Through every step of the journey we the book. I am a data scientist, and still I
have only one thing in mind: what are the did not know how to understand the num-
oddsofbeatingthismonster?Howlongwill bers. I wanted a miracle, and unfortunately
xi
xii
Preface
the miracle did not happen for us. So, I will the time to review this book before being
saythat thisbook isdedicated to my father, published, and more especially for always
andtoallthepeoplethatarestrugglingwith being my friend. Last but not least, I would
thisdisease,mayyousucceedinyourbattle, liketothankmyfamilyfortheirunderstand-
and to those who have lost the battle, may ing,love, and unconditional support.
you allrestin peace. As a final note, thank you Dad for being
I want to express my gratitude to Rafael my mentor, my friend, and for teaching me
Teixeira and Samuel Young for offering me Statistics. Until we meet again, may God
this great opportunity of writing this book, hold yougentle in thepalm ofHishand.
and who so warmly sustained this project.
Many thanks go out to Prof. Sally McClean Smaranda Belciug
for always supporting me, and for taking Craiova, Romania
C H A P T E R
1
Life challenge. Cancer
1.1 Cancer throughout history
CancerseemslikeaRussianroulette.Itislikeeverydayyouhearthatsomeoneyouknowor
heardofhasjustbeendiagnosedwithit.Itisscary.Youfeelinsecureandthinkthatyoumight
benext.Youcomfortyourselfwiththoughtsthatyouoryourfamilywon’tget“hit”byit.You
eattherightfood,exercise,sleepwell,takeyourmineralsandvitamins,youdonotsmoke,nor
drink,andmaybe,justmaybe,youhavenofamilyhistoryrecordswithit.Still,youmighthave
heardofpeoplethatneversmoked,neverate“bad”food,werefit,andZen,andstillgotcancer.
Alarmiststhatsaythatthecancerratesaregoingupfuelallthesethoughts.Aretheyright,orare
theyjustaddingfiretothegeneralparanoia?Shouldyouliveinfear?Webelievenot.Doesour
answer mean that you will live a long and healthy life, cancer free? Not quite. According to
http://ourworldindata.org/cancer(AccessedMay3,2019),canceristhesecondleadingcause
of death, after cardiovascular diseases. The Institute for Health Metrics and Evaluation
(IHME)—https://www.healthdata.org (Accessed May 3, 2019) states that in 2017 between
9.2and9.7milliondeathswerecausedbyvariousformsofcancer.So,thingsarenotlooking
great.Now,thealarmistsstepinandsaythatinthepasttherateswerelower.Thatmaybetrue,
butweshouldtakeintoaccountthefactthatnowadaysthroughscreeningtestsandnewAr-
tificialIntelligence(AI)technologywedetectcancermore.Thus,beforeembarkingonourcan-
cer history trip, we suggest that you take a deep breath, relax, and enjoy the moment. Carpe
diem!Youneverknowwhatmightcomenext,sodonotwasteyourtimefearingit,“Whatmust
be,shallbe”—Juliet,fromWilliamShakespeare’sRomeoandJuliet.
There are many types of cancer. Cancer can begin in any part of the body. The moment
when a cell starts growing out of control and starts crowding out the healthy cells, that is
where it all begins. Due to the fact that any cell can become cancerous implies the fact that
cancerisnotjustasingledisease.Cancercanstartinanyorgan,orevenintheblood.Cancer
that starts in the same type of cells are somehow alike, but still they are different in what
regards their speedofgrowthandspread.Thatiswhatmakeseachcancerunique,andtai-
lored accordinglyto the person that has it.
Cancerdevelopsinanylivingorganism,whetheritisahumanbeingorananimal.Someof
the first proofs of cancer have been found in Ancient Egypt among fossilized bone tumors.
1
ArtificialIntelligenceinCancer:DiagnostictoTailoredTreatment #2020ElsevierInc.Allrightsreserved.
https://doi.org/10.1016/B978-0-12-820201-2.00001-5
2
1. Lifechallenge.Cancer
Osteosarcoma,orbonecancer,hasbeendiscoveredinmummies(HamadaandRida,1972).In
1862,atLuxor,EdwinSmith,anAmericanEgyptologist,cameintocustodyofamedicalpa-
pyrusthatwasnamedafterhisowner—theEdwinSmithPapyrus.TheEdwinSmithPapyrusis
the oldest known medical recording that dates back into 1700 BC, and it is thought to be a
copy of the original manuscript dated in 3000 BC. It has 4.68m in length and it is divided
in17pages.In1906,Smith’sdaughtergavethepapyrustotheNewYorkHistoricalSociety.
The Edwin Smith Papyrus is a surgical document. In it, there are described eight cases of
breasttumorsorulcerationsthatwereremovedthroughcauterizationwiththeuseofatool
called fire drill. Regarding this disease it is written, “There is no treatment”. Georg Moritz
Ebers, a German Egyptologist and novelist, acquired another ancient papyrus, in Thebes
in 1872. The Ebers papyrus dates back from 1500 BC, and included information regarding
anincurablediseasethatproducedtumorsfoundinskin,uterus,stomach,andrectum.Com-
paredtotheEdwinSmithpapyrus,thispapyrusismedical,describingpharmacological,me-
chanical and magical treatments (Haas, 1999). An example of a cancer remedy is: when
dealingwith“atumoragainsttheGodXenus”therecommendationis“dothounothingthere
against” (Hajdu, 2011).
Around 400 BC, Hippocrates named the non-ulcer forming and ulcer-forming tumors
carcinosandcarcinomaaftertheGreekwordfor“crab.”RememberthatitwasKarkinos,also
knownasCarcinus,thegiantcrabthathelpedHydrainthelegendbattlewithHerakles(or
Hercules) at Lerna. Even if Herackles’ foot crushed Karkinos, the goddess Hera placed it
amongstthestars,astheconstellationcancer.Therearesomeexplanationstowhyhechose
thisname:(a)malignanttumorstogetherwiththeirbloodvesselsthathaveswollen,itsad-
herents,resemblethepictureofacrabwithitslegsspreadinacircle;(b)malignanttumors
havehardtissuethatremindsofthehardnessofthecrab’sshell,and(c)thepaincausedbythe
tumor can beassociated with the pinch o a crab’s claw (Hajdu, 2011; Mitrus et al., 2012).
In what regards the term “oncology,” the name comes from the Ancient Greek word
“onkos”atragicmaskwornintheaterplaysthatsymbolizedtheburdenscarriedbytheper-
sonwhoworeit.Ontheotherhand,oncosinGreekmeansswelling.Aroundtheyear200AD,
theGreekphysicianGalenintroducedthemedical termonkosfor alltumor types, whether
they were malignant or benign.
As time passed by and Rome had fallen, Galen’s teachings regarding cancer started to
reach physicians inConstantinople, Cairo, Alexandria, and Athens. While in the West, sor-
cerywasusedtocurediseases,inthispartoftheworldscientistsweretryingtounderstand
and explain cancer. They agreed with Hippocrates’ conclusions that cancer was a result of
excessofblackbile(amedievalbeliefthatahumorsecretedbykidneysorspleenthatcaused
melancholy—according to Merriam Webster dictionary—https://www.merriam-webster
.com/dictionary/black%20bile—AccessedMay2,2019).Hippocrateshypothesizedthatcan-
cerwascorrelatedtotheimbalanceofthefourbodyhumors:blood,phlegm,yellowbile,and
blackbile.Theyalsonotedthatcancerwascurableonlyinitsearlieststages.Thetreatment
was based on arsenic.
Fastforwarding totheMiddleAges,duetoreligiousbeliefsthatforbiddedscientificim-
provement, cancer was supposedlybe aninfectiousdisease.
The excess of black bile idea continued to be present until the 16th century. During the
Renaissance, scientists started performing autopsies (remember Rembrandt’s The Anatomy
Lesson of Dr. Nicolaes Tulp). Andreas Vesalius, a 16th century anatomist, demonstrated that