Cancer Association of South Africa (CANSA)

Transcription

1 Cancer Assciatin f Suth Africa (CANSA) Fact Sheet n Lung Cancer Intrductin The chest cntains tw lungs, ne lung n the right side f the chest, the ther n the left side f the chest. Each lung is made up f sectins called lbes the right lung cnsists f three lbes and the left lung cnsists f tw lbes. The lung is sft and prtected by the ribcage. The purpses f the lungs are t absrb xygen (O2), int the bldstream fr distributin thrughut the bdy and t remve carbn dixide (CO2), a waste prduct, frm the bdy. [Picture Credit Anatmy f the Lungs] Lung Cancer Lung cancer is a disease characterised by uncntrlled cell grwth in tissues f the lung. If left untreated, this grwth can spread beynd the lung in a prcess called metastasis int nearby tissue and, eventually, int ther parts f the bdy. Mst cancers that start in lung, knwn as primary lung cancers, are carcinmas that derive frm epithelial cells. Incidence f Lung Cancer in Suth Africa Accrding t the Natinal Cancer Registry (2013) the fllwing number f lung cancer cases was histlgically diagnsed in Suth Africa during 2013: Octber 2017 Page 1

2 Grup - Males 2013 Actual N f Cases Estimated Lifetime Risk Percentage f All Cancers All males :76 4,91% Asian males 80 1:59 9,65% Black males 691 1:131 6,42% Clured males 361 1:35 8,65% White males 636 1:47 3,15% Grup - Females 2013 Actual N f Cases Estimated Lifetime Risk Percentage f All Cancers All females 923 1:205 2,52% Asian females 33 1:179 3,15% Black females 241 1:547 1,54% Clured females 207 1:78 5,09% White females 443 1:78 2,79% The frequency f histlgically diagnsed cases f lung cancer in Suth Africa fr 2013 was as fllws (Natinal Cancer Registry, 2013): Grup - Males All males Asian males Black males Clured males White males Grup - Females All females Asian females Black females Clured females White females N.B. In the event that the ttals in any f the abve tables d nt tally, this may be the result f uncertainties as t the age, race r sex f the individual. The ttals fr all males and all females, hwever, always reflect the crrect ttals. Types f Lung Cancer There are tw main types f lung cancer, nn-small cell lung cancer and small cell lung cancer. These names refer t hw the cancers lk under a micrscpe t a pathlgist. Mst lung cancers are nn-small cell. There are subtypes f nn-small cell lung cancer. Because different types f lung cancer are treated differently, an nclgist will determine exactly what treatment is best. Nn-Small Cell Lung Cancer (NSCLC) NSCLC accunts fr abut 80% f lung cancers. There are different types f NSCLC, including: Octber 2017 Page 2

3 Squamus cell carcinma (als called epidermid carcinma) - this is the mst cmmn type f NSCLC. It frms in the lining f the brnchial tubes and is the mst cmmn type f lung cancer in men. Adencarcinma - this cancer is fund in the glands f the lungs that prduce mucus. This is the mst cmmn type f lung cancer in wmen and als amng peple wh have nt smked. Brnchi-alvelar carcinma - this is a rare subset f adencarcinma. It frms near the lungs' air sacs. Recent clinical research has shwn that this type f cancer respnds mre effectively t the newer targeted therapies. Large-cell undifferentiated carcinma - this cancer frms near the surface, r uter edges, f the lungs. It can grw rapidly. Small Cell Lung Cancer (SCLC) SCLC accunts fr abut 20% f all lung cancers. Althugh the cells are small, they multiply quickly and frm large tumurs that can spread thrughut the bdy. Smking is almst always the cause f SCLC. There are tw types f SCLC. The cancer cells f each type grw and spread in different ways. The types f small cell lung cancer are named fr the kinds f cells fund in the cancer and hw the cells lk when viewed under a micrscpe: Small cell carcinma (at cell cancer) Cmbined small cell carcinma (LungCancer.Org; May Clinic; Natinal Cancer Institute). Causes f Lung Cancer Lung cancer has always been and still is mre cmmn in men. As mre wmen have started smking, the number f wmen develping lung cancer has been n the increase. Peple wh d nt smke can als develp lung cancer. Apprximately 10 15% f peple wh get lung cancer have never smked. Other risk factrs include the effects f past cancer treatment and expsure t asbests, radn gas and in very rare cases substances such as uranium, chrmium and nickel. Lung cancer is nt infectius and can t be passed n t ther peple. Smking - The mre ne smkes, the greater the risk f develping lung cancer. It is als mre likely t develp in peple wh start smking at a yung age. If smene stps smking, their risk f develping lung cancer falls quite quickly. After abut 15 years, the chance f develping the disease is similar t that f a nn-smker. This sectin n smking includes the use f: Hkah e-hkah Octber 2017 Page 3

4 In the event f smene quitting t smke, psitive health benefits can immediately be experienced. The fllwing indicates the health benefits that can be expected upn quitting the habit f smking: Within: 20 minutes - the bld pressure, pulse rate and the temperature f ne s hands and feet have returned t nrmal 8 hurs the remaining nictine in ne s bldstream will have fallen t 6.25% f nrmal peak daily levels, a 93.75% reductin 12 hurs - bld xygen level will have increased t nrmal and carbn mnxide levels will have drpped t nrmal 72 hurs One s entire bdy will test 100% nictine-free and ver 90% f all nictine metablites (the chemicals it breaks dwn int) will nw have passed frm the bdy via ne s urine. Symptms f chemical withdrawal have peaked in intensity, including restlessness. The number f cue induced crave episdes experienced during any quitting day will peak fr the average ex-user. Lung brnchial tubes leading t air sacs (alveli) are beginning t relax in recvering smkers. Breathing is becming easier and the lung's functinal abilities are starting t increase 5-8 days - the average ex-smker will encunter an average f three cue induced crave episdes per day. Althugh we may nt be average and althugh serius cessatin time distrtin can make minutes feel like hurs, it is unlikely that any single episde will last lnger than 3 minutes. Keep a clck handy and time them. 2 t 4 weeks - cessatin related anger, anxiety, difficulty cncentrating, impatience, insmnia, restlessness and depressin have ended. If still experiencing any f these symptms get seen and evaluated by yur physician 8 weeks - insulin resistance has nrmalised despite average weight gain f 2.7 kg (1997 study). 1 year - the excess risk f crnary heart disease, heart attack and strke have drpped t less than half that f a smker 5 years - the risk f a subarachnid haemrrhage has declined t 59% f previus risk while still smking (2012 study). In a female ex-smker, the risk f develping diabetes is nw that f a nn-smker (2001 study) 5 t 15 years - the risk f strke has declined t that f a nn-smker 10 years - the risk f being diagnsed with lung cancer is between 30% and 50% f that fr a cntinuing smker (2005 study). Risk f death frm lung cancer has declined by almst half fr an average smker (ne pack per day). Risk f cancer f the muth, thrat, esphagus and pancreas have als declined. Risk f develping diabetes fr bth men and wmen is nw similar t that f smene wh never smked (2001 study) 15 years - the risk f crnary heart disease is nw that f a persn wh has never smked. The risk f pancreatic cancer has declined t that f smene wh never smked (2011 study (WhyQuit). In a recent study by Alexandrv, et al., (2016) their analysis shws a direct link between the number f cigarettes smked in a lifetime and the number f mutatins in tumur DNA. The researchers fund that, n average, smking a packet f cigarettes a day led t: 150 mutatins in each lung cell every year 97 in the larynx r vice bx 23 in the muth 18 in the bladder Octber 2017 Page 4

5 six in the liver Accrding t the researchers, the mre mutatins there are, the higher the chance that these will ccur in the key genes that are called cancer genes, which cnvert a nrmal cell int a cancer cell. Passive smking- breathing in ther peple s cigarette smke (passive smking) increases the risk f lung disease and cancer Pipes and cigars - althugh pipe and cigar smkers have a lwer risk f lung cancer than cigarette smkers, they are still at a much greater risk fr lung cancer than nn-smkers with an increased risk f cancer f the lip Cannabis - Cannabis smke cntains a similar prfile f carcingenic (cancer causing) chemicals as tbacc smke and is inhaled mre deeply. Althugh cannabis smke is knwn t cntain similar harmful and carcingenic substances t tbacc smke, relatively little is still currently understd regarding the respiratry health effects frm cannabis smking (Gates, et al.). Radiatin therapy t the Chest - cancer survivrs wh had radiatin therapy t the chest are at higher risk f lung cancer. Patients at highest risk include thse treated fr Hdgkin disease and wmen with breast cancer treated with radiatin after a mastectmy (but nt a lumpectmy) Radn gas radn is a clurless, durless radiactive gas that frms frm the decay f radiactive elements such as uranium. The radn gas given ff by sil and rck can enter hmes and buildings thrugh cracks in flrs and walls, pipe, wires and pumps. Radn cncentratins are usually highest in basements r in undergrund mining envirnments. It can als be released frm undergrund water supplies in small amunts. Expsure can als ccur frm building materials made frm radn cntaining substances. Expsure t high cncentratins f radn can increase the risk fr develping lung cancer. It is believed that apprximately 9% f lung cancers may be caused by expsure t radn. Smking, radn, and secndhand smke are the leading causes f lung cancer. Radn is the number ne cause f lung cancer amng nn-smkers, accrding t Envirnmental Prtectin Agency (EPA) estimates. Overall, radn is the secnd leading cause f lung cancer Age - like mst types f cancer, lung cancer is mre cmmn in lder peple. Abut 80% f lung cancers are diagnsed in peple ver 60. Lung cancer rarely affects peple under 40 Genetic risk - sme peple with a clse relative wh has had lung cancer may be at an increased risk f it themselves, althugh the increase in risk is very small. The risk is slightly greater if a relative is a nn-smker and develped lung cancer at an early age, r if mre than ne relative n the same side f the family develped lung cancer If cncerned abut a family histry f lung cancer, it helpful t read ur mre detailed infrmatin abut genetic risk r talk t a medical practitiner r health prfessinal Asbests - peple wh have been in prlnged r clse cntact with asbests have a higher risk f develping lung cancer, especially smkers. Asbests and tbacc smke act tgether t increase the risk. Many peple have been in cntact with asbests during their Octber 2017 Page 5

6 wrking lives. Lw-level expsure increases the risk f lung cancer nly slightly (cmpared t the risk frm smking), while heavy expsure may result in a much higher risk. If a persn has wrked with asbests and develp lung cancer, he/she may be able t claim cmpensatin r be paid Industrial Injuries Disablement Benefit. Mre advice can be btained frm a treating dctr, a cancer supprt rganisatins r by calling ur cancer supprt specialists. Asbests expsure als increases the risk f mesthelima, a cancer f the membranes which cver the lungs. Industrial expsure - several industrial carcingens, fr example, arsenic and plycyclic hydrcarbns as well as sme ccupatins including nn-ferrus metal prductin and painting, have been linked t lung cancer Expsure t Diesel Exhaust Fumes - diesel exhaust was classified as a cause f lung cancer by the Internatinal Agency fr Research n Cancer (IARC) in June 2012, fllwing a review f evidence mainly frm highly-expsed wrkers. IARC cited a study f diesel exhaust expsure in miners, which shwed risk f lung cancer was increased apprximately three times in thse mst heavily expsed Expsure t herbicides and insecticides - the large American Prspective Agricultural Health Study Expsure suggests that expsure t herbicides and insecticides increases lung cancer risk Occupatinal expsure t silica - silica expsure can result in silicsis with an increased risk fr lung cancer, but withut silicsis there is n increased risk. The bdy f evidence supprts an increased risk f lung cancer with expsure t asbests in nn-smkers and that risks are especially high in thse wh smke, wh als have past expsure t asbests Family Histry - a family histry f lung cancer in a first-degree relative is assciated with a tw-fld (duble) increased risk, independent f smking. If bth cancers are diagnsed befre the age f 60, the risk rati is almst five-fld. The assciatin between family histry and risk may be strnger in black individuals than white Past cancer treatment - peple wh have been treated fr sme types f cancer may have a slightly increased risk f develping lung cancer many years later. Wmen wh were treated with raditherapy fr breast cancer and wh smke may have an increased risk f lung cancer. Peple wh have been treated fr sme types f lymphma using raditherapy t the chest area as well as men wh have been treated fr testicular cancer using raditherapy t the chest area, have a slightly increased risk f lung cancer, especially if they smke. Hwever, the risk f develping lung cancer is far utweighed by the benefits f the initial treatment Diet - scientists are studying many different fds and dietary supplements t see whether they increase the risk f getting lung cancer. It is knwn that smkers wh take betacartene supplements have increased risk f lung cancer. Beta-cartene is an antixidant. It prtects the bdy frm damaging mlecules called free radicals. Free radicals damage cells thrugh a prcess knwn as xidatin. Over time, this damage can lead t a number f chrnic illnesses. There is gd evidence that eating mre antixidants fds helps bst yur immune system, prtect against free radicals, and may Octber 2017 Page 6

7 lwer yur risk f heart disease and cancer. But the issue is a little mre cmplicated when it cmes t taking antixidant supplements. Studies that lk at big grups f peple suggest that thse wh eat 4 r mre daily servings f fruits and vegetables rich in beta-cartene may reduce their risk f develping heart disease r cancer. Fds rich in beta-cartene include thse that are range r yellw, such as peppers, squashes, and carrts. A few studies have fund that peple wh take beta-cartene supplements may have a higher risk fr cnditins such as cancer and heart disease. Researchers think that may be because the ttal f all the nutrients yu eat in a healthy, balanced diet gives mre prtectin than just beta-cartene supplements alne. There is als sme evidence that when smkers and peple wh are expsed t asbests take beta-cartene supplements, their risk f lung cancer ges up. Fr nw, smkers shuld nt take beta-cartene supplements (University f Maryland Medical Center). HIV and Aids - significant increases in risk f lung cancer have been reprted in research studies cnducted amng peple with HIV and Aids even after accunting fr smking, althugh ne study shwed an assciatin in men nly Chlamydia Pneumniae - peple with antibdies t Chlamydia pneumniae have shw an increase in risk fr lung cancer. Chlamydia pneumniae is an infectius bacteria assciated with a number f diseases including pneumnia Systemic Lupus Erythematsus - an increased risk f lung cancer has been shwn in peple with systemic Lupus Erythematsus Klinefelter syndrme Klinefelter syndrme has been shwn t be a risk factr althugh the risk is less than tw-fld Tuberculsis - a systematic review f published studies shwed that the risk fr lung cancer is almst dubled fr peple with a previus diagnsis f tuberculsis (TB), after taking int accunt smking histry. The risk increase persisted fr mre than 20 years after TB diagnsis (MacMillan Cancer Supprt; WebMD; Centers fr Disease Cntrl and Preventin; Cancer Research UK; United States Envirnmental Prtectin Agency). Screening fr Lung Cancer Screening examinatins are tests perfrmed t find disease befre symptms begin. The gal f screening is t detect disease at its earliest and mst treatable stage. In rder t be widely accepted and recmmended by medical practitiners, a screening prgram must include reducing the number f deaths frm the given disease. Screening tests may include labratry tests t check bld and ther fluids, genetic tests that lk fr inherited genetic markers linked t disease, and imaging tests that prduce pictures f the inside f the bdy. In lung cancer screening, individuals wh have a high risk f develping lung cancer but n signs r symptms f the disease underg Lw Dse Cmputed Tmgraphy (LDCT) scanning f the chest. Octber 2017 Page 7

8 Lung Cancer (LC) is a deadly malignancy. Until recently, there was n prven methd fr early detectin, but with the advent f Lw Dse Cmputed Tmgraphy (LDCT) screening, there is the ptential t save lives in high-risk individuals by detecting and treating earlystage disease. Hwever, the false-psitive rate fr LC screening is high and the ptential benefits may be diminished if screening results in increased mrbidity and mrtality related t increased frequency f invasive prcedures. Refinement f eligibility criteria and the use f structured, standardised reprting fr CT interpretatin may mitigate risk by reducing the number f false-psitives identified n screening. A well-defined prtcl fr management f screen-detected pulmnary ndules is a vital cmpnent f any LC screening prgramme and may aid in minimising unnecessary surgery. Successful implementatin f LC screening relies n a cmprehensive, multidisciplinary prgramme with an emphasis n smking cessatin and LC preventin. Balanced presentatin f ptential benefits, harms and csts f screening, such that individuals are able t make infrmed decisins abut their healthcare chices, is f the utmst imprtance and risk-predictin mdels may be f use in facilitating these discussins. Suth Africa faces unique challenges in implementing LC screening. Identificatin f risk factrs that are particularly relevant t the lcal ppulatin (e.g. HIV infectin, silica expsure and bimass emissins expsure) is an area where future research is required. Limited resurces in the state sectr and restricted funding by medical aids in the private sectr bth pse significant barriers t the equitable implementatin f LC screening in Suth African cmmunities. Cllatin f cmprehensive lcal LC data and engaging the relevant rleplayers in discussin will be imprtant initial steps twards planning a LC screening prgramme in the lcal setting. Current criteria f wh shuld have an annual LDCT: Individuals at risk fr develping lung cancer Smkers between the ages f Current smkers r thse wh have quit smking within the last 15 years Individuals wh have a tbacc smking histry f at least 30 "pack years" (an average f ne pack a day fr 30 years) T translate smking histry int 'pack years, simply multiply the number f cigarette packs smked per day by the number f years ne has smked. Fr example: 1½ packs a day smked ver a 30-year perid = 45 pack years. Hw Lung Cancer Screening is Perfrmed Cmputerised Tmgraphy (CT) scanning wrks like ther X-ray examinatins. X-rays are a frm f radiatin that can be directed thrugh the part f the bdy being examined. Different bdy parts absrb the X-rays t varying degrees. With CT scanning, numerus X-ray beams and a set f electrnic x-ray detectrs rtate arund the patient, measuring the amunt f radiatin being absrbed thrughut the bdy. At the same time, the examinatin table is mving thrugh the scanner, s that the x-ray beam fllws a helical path. A special cmputer prgram prcesses this large vlume f data t create tw-dimensinal crss-sectinal images f the bdy, which are then displayed n a mnitr. This technique is called helical r spiral CT. Octber 2017 Page 8

9 Fr chest CT, the technlgist will psitin the individual n the examinatin table, usually lying flat n his/her back r less cmmnly, n his/her side r n his/her stmach. Straps and pillws may be used t help maintain the crrect psitin and t help the patient remain still during the exam. [Picture Credit: Cmputed Tmgraphy] The patient will usually be asked t raise his/her arms ver his/her head. Next, the table will mve quickly thrugh the scanner t determine the crrect starting psitin fr the scans. Then, the table will mve slwly thrugh the machine as the actual CT scanning is perfrmed while the patient hlds his/her breath fr the shrt five t 10 secnd scan. Benefits and Risks f Lung Cancer Screening Benefits f lung cancer screening include: Because Cmputerised tmgraphy (CT) scans are able t detect even very small ndules in the lung, Lw Dse Cmputed Tmgraphy (LDCT) f the chest is especially effective fr diagnsing lung cancer at its earliest, mst treatable stage. CT is fast, which is imprtant fr patients wh have truble hlding their breath. CT scanning is painless and nn-invasive. N radiatin remains in a patient's bdy after a CT examinatin. X-rays used in LDCT f the chest have n immediate side effects. Lw-dse CT scans f the chest prduce images f sufficient image quality t detect many abnrmalities using up t 90 percent less inizing radiatin than a cnventinal chest CT scan. Lung cancer screening with LDCT has been prven t reduce the number f deaths frm lung cancer in patients at high risk. Lung cancer fund by screening with LDCT is ften at an earlier stage f disease. When cancer is fund with screening, patients can mre ften underg minimally invasive surgery and have less lung tissue remved. Ptential risks f lung cancer screening include: False psitive results ccur when a test appears t be abnrmal but n lung cancer is fund. Abnrmal findings may require additinal testing t determine whether r nt cancer is present. These tests, such as additinal CT exams r mre invasive tests in which a piece f lung tissue is remved (called a bipsy), have risks and may cause a patient anxiety. Test results that appear t be nrmal even when lung cancer is present are called false-negative results. A persn wh receives a false-negative test result may delay seeking medical care. Octber 2017 Page 9

10 Nt all f the cancers detected by LDCT will be fund in the early stage f the disease. Screening that detects lung cancer may nt imprve ne s health r help ne live lnger if the disease has already spread beynd the lungs t ther places in the bdy. LDCT lung cancer screening and all ther screening examinatins can lead t the detectin and treatment f cancer which may never have harmed ne. This can result in unnecessary treatment, cmplicatins, and cst. Health insurance cmpanies may nly cver the cst f an LDCT scan t screen fr lung cancer in patients wh meet certain criteria. There is a theretical small risk f cancer frm expsure t lw dse radiatin. (Schar, 2015; RadilgyInf.rg). Signs and Symptms f Lung Cancer Lung cancer typically desn't cause signs and symptms in its earliest stages. Signs and symptms f lung cancer typically ccur nly when the disease is advanced. Signs and symptms f lung cancer may include: a new cugh that desn't g away changes in a chrnic cugh r smker's cugh a cugh that gets wrse r des nt g away cughing up bld, even a small amunt shrtness f breath r wheezing cnstant chest pain especially when cughing frequent chest infectins, such as pneumnia, r an infectin that des nt g away wheezing harseness swelling f the neck and face fatigue (feeling very tired all the time) lss f appetite lsing weight withut trying bne pain headache (May Clinic; Canadian Cancer Sciety; NIH Senir Health). Diagnsis f Lung Cancer The fllwing are used t diagnsed cancer f the lung: Medical histry - t find ut if lung cancer may be present, the dctr evaluates a persn's medical histry, smking histry, his/her expsure t envirnmental and ccupatinal substances, and family histry f cancer. Physical examinatin - the dctr als perfrms a physical exam and may rder a test t take an image f the chest r ther tests. Seeing a spt n an image is usually hw a dctr first suspects that lung cancer may be present. Octber 2017 Page 10

11 Sputum cytlgy - if lung cancer is suspected, the dctr may rder a test called a sputum cytlgy. This is a simple test where a dctr examines a sample f mucus cells cughed up frm the lungs under a micrscpe t see if cancer is present. Bipsy - but t cnfirm the presence f lung cancer, the dctr must examine fluid r tissue frm the lung. This is dne thrugh a bipsy - the remval f a small sample f fluid r tissue fr examinatin under a micrscpe by a pathlgist t cnfirm the presence f lung cancer. Brnchscpy a prcedure t cllect cells r small samples f tissues frm the airways and lungs. The dctr inserts a brnchscpe, a thin, lighted tube, int the muth r nse and dwn thrugh the windpipe t lk int the airways t cllect any samples f tissue cells if needed. Needle aspiratin - the dctr numbs the chest area and inserts a thin needle thrugh the chest wall int the tumur t remve a sample f tissue. Thracentesis - using a needle, the dctr remves a sample f the fluid that surrunds the lungs t check fr cancer cells. Thractmy - surgery t pen the chest is smetimes needed t diagnse lung cancer. This prcedure is a majr peratin perfrmed in a hspital. Imaging tests - dctrs use imaging methds such as a spiral Cmputerised Tmgraphy (CT) scan als cmmnly knwn as helical C) r a Psitrn Emissin Tmgraphy (PET) scan t lk fr signs f cancer. A CT scan is a series f detailed pictures f areas inside the bdy. A PET scan is a cmputerised image f the metablic activity f bdy tissues. Other tests - this includes remval f lymph ndes fr examinatin under a micrscpe t check fr cancer cells. Lymph ndes are small, bean-shaped structures fund thrughut the bdy that filter substances in a fluid called lymph and help fight infectin and disease. (NIH Senir Health; WebMD). Staging f Lung Cancer Staging is the prcess f finding ut hw far a cancer has spread. This is imprtant because treatment ptins and utlk fr recvery and survival depend n the cancer's stage. Staging f lung cancer uses a system created by the American Jint Cmmittee n Cancer (AJCC). The TNM system The TNM system fr staging cntains 3 key pieces f infrmatin: T describes the size f the primary tumur, measured in centimetres (cm), and whether the cancer has spread t rgans next t the tumur N describes the extent f spread t nearby (reginal) lymph ndes M indicates whether the cancer has metastasised (spread) t ther rgans f the bdy Numbers r letters appear after T, N, and M t prvide mre details abut each f these factrs: Octber 2017 Page 11

12 the numbers 0 thrugh 4 indicate increasing severity the letter X means cannt be assessed because the infrmatin is nt available the letters is mean carcinma in situ, which means the tumur is cntained within the tp layer f anal tissue and has nt yet reached deeper layers f tissue TX T0 Tis T1 T2 T3 T4 primary tumur cannt be assessed, r tumur prven by the presence f malignant cells in sputum r brnchial washings but nt visualised by imaging r brnchscpy n evidence f primary tumur carcinma in situ tumur 3cm r less in greatest dimesin, surrunded by lung r visceral pleura, withut brnchscpic evidence f invasin mre prximal than the lbar brnchus tumur with any f the fllwing features f size r extent: mre than 3cm in greatest dimensin invlving main brnchus, 2cm r mre distal t the carina invading the visceral pleura assciated with atelectasis r bstructive pneumnitis that extends t the hilar regin (area between the tw lungs) but des nt invlve the entire lung tumur f any size that: directly invades the chest wall (including superir sulcus tumurs), diaphragm, mediastinal r parietal pericardium is lcated in the main brnchus less than 2cm distal t the carina but withut invlvement f the carina is assciated with atelectasis r bstructive penumnitis f the entire lung tumur f any size that: invades the mediastinum, heart, great vessels, trachea, esphagus, vertebral bdy r carina is assciated with a malignant pleural effusin Reginal Lymph Ndes (N) NX reginal lymph ndes cannt be assessed N0 n reginal lymph ndes metastasis N1 metastasis in ipsilateral peribrnchial and/r ipsilateral hilar lymph ndes, including direct extensin N2 metastasis in ipsilateral mediastinal and/r subcarinal lymph nde(s) N3 metastasis in cntralateral mediastinal, cntralateral hilar, ipsilateral r cntralateral scalene r supraclavicular lymph nde(s) Distant Metastases (M) MX presence f distant metastasis cannt be assessed M0 n distant metastasis M1 distant metastasis Stage Gruping Occult TX N0 M0 Stage 0 Tis N0 M0 Stage I T1 N0 M0 T2 N0 M0 Octber 2017 Page 12

13 Stage II T1 N1 M0 T2 N1 M0 Stage IIIA T1 N2 M0 T2 N2 M0 T3 N0 M0 T3 N1 M0 T3 N2 M0 Stage IIIB Any T N3 M0 T4 Any N M0 Stage IV (CTSN) Any T Any N M1 Where Lung Cancer May Spread t in the Bdy In the event f lung cancer spreading t ther parts f the bdy, it may spread as indicated in the bld sectin belw: Cancer Type: Bladder Breast Cln Clrectal Kidney Lung Melanma Ovary Pancreas Prstate Stmach Thyrid Uterus Nn-melanma skin cancer (Natinal Cancer Institute) Main Sites f Metastasis (Spread) Bne, liver, lung Bne, brain, liver, lung Liver, lung Liver, lung, peritneum (lining f abdmen) Adrenal gland, bne, brain, liver, lung Adrenal gland, bne, brain, liver, ther lung Bne, brain, liver, lung, skin, muscle Liver, lung, peritneum (lining f abdmen) Liver lung, peritneum (lining f abdmen) Adrenal gland, bne, liver, lung Liver, lung, peritneum (lining f abdmen), varies Bne, liver, lung Bner, liver, lung, peritneum (lining f abdmen), vagina Very rare: lymph ndes, lung, bne (if in head/neck regin) Treatment f Lung Cancer The type f treatment a patient will receive fr lung cancer depends n several factrs, including: the type f lung cancer (nn-small cell r small cell) the size and psitin f the cancer hw far advanced the cancer is (the stage) patient s verall health Deciding what treatment is best can be difficult. The cancer team will make recmmendatins, but the final decisin will be that f the patient. Treatment ptins include: Octber 2017 Page 13

14 surgery raditherapy chemtherapy Small Cell Lung Cancer (SCLC) Fr mst patients with small cell lung cancer, current treatments d nt cure the cancer. Regardless f stage, the current prgnsis fr patients with SCLC is pr despite imprvements in diagnsis and therapy made during the past 25 years. Withut treatment, SCLC has the mst aggressive clinical curse f any type f pulmnary tumur, with median survival frm diagnsis f nly 2 t 4 mnths. Abut 10% f the ttal ppulatin f SCLC patients remains free f disease during the 2 years frm the start f therapy, which is the time perid during which mst relapses ccur. Even these patients, hwever, are at risk f dying frm lung cancer (bth small and nn-small cell types).] The verall survival at 5 years is 5% t 10%. (NHS Chices; Natinal Cancer Institute) Nn-Small Cell Lung Cancer Nine types f standard treatment are used: Surgery Five types f surgery are used t treat lung cancer: Wedge resectin remval f a tumur and sme f the nrmal tissue arund it. When a slightly larger amunt f tissue is taken, it is called a segmental resectin. Segmental resectin f the lung - part f the lung lbe cntaining the cancer and a slightly larger amunt f healthy tissue arund it is remved than in the case f a wedge resectin Lbectmy remval f a whle lbe (sectin) f the lung Pneumnectmy remval f the whle lung Sleeve resectin remve f part f the brnchus Even if the dctr remves all the cancer that can be seen at the time f the surgery, sme patients may be given chemtherapy r radiatin therapy after surgery t kill any remaining cancer cells. Treatment given after the surgery t lwer the risk f recurrence, is called adjuvant therapy. Radiatin therapy - radiatin therapy is a cancer treatment that uses high-energy x-rays r ther types f radiatin t kill cancer cells r keep them frm grwing. There are tw types f radiatin therapy. External radiatin therapy uses a machine utside the bdy t send radiatin tward the cancer. Internal radiatin therapy uses a radiactive substance sealed in needles, seeds, wires, r catheters that are placed directly int r near the cancer. Radisurgery - is a methd f delivering radiatin directly t the tumur with little damage t healthy tissue. It des nt invlve surgery and may be used t treat certain tumurs in patients wh cannt have surgery. Octber 2017 Page 14

15 The way the radiatin therapy is given depends n the type and stage f the cancer being treated. It als depends n where the cancer is fund. Fr tumurs in the airways, radiatin is given directly t the tumur thrugh an endscpe. Chemtherapy - chemtherapy is a cancer treatment that uses drugs t stp the grwth f cancer cells, either by killing the cells r by stpping them frm dividing. When chemtherapy is taken by muth r injected int a vein r muscle, the drugs enter the bldstream and can reach cancer cells thrughut the bdy (systemic chemtherapy). When chemtherapy is placed directly int the cerebrspinal fluid, an rgan, r a bdy cavity such as the abdmen, the drugs mainly affect cancer cells in thse areas (reginal chemtherapy). The way the chemtherapy is given depends n the type and stage f the cancer being treated. Targeted therapy - targeted therapy is a type f treatment that uses drugs r ther substances t identify and attack specific cancer cells withut harming nrmal cells. Mnclnal antibdies and tyrsine kinase inhibitrs are tw types f targeted therapy being used in the treatment f nn-small cell lung cancer. Mnclnal antibdy therapy - is a cancer treatment that uses antibdies made in the labratry frm a single type f immune system cell. These antibdies can identify substances n cancer cells r nrmal substances that may help cancer cells grw. The antibdies attach t the substances and kill the cancer cells, blcking its grwth, r keeping it frm spreading. Mnclnal antibdies are given by infusin. It may be used alne r t carry drugs, txins, r radiactive material directly t cancer cells. Mnclnal antibdies used t treat nn-small cell lung cancer include bevacizumab and cetuximab. Bevacizumab binds t vascular endthelial grwth factr (VEGF) and may prevent the grwth f new bld vessels that tumurs need t grw. Cetuximab binds t epidermal grwth factr receptr (EGFR) and wrks t stp cancer cells frm grwing and dividing. Tyrsine kinase inhibitrs - are targeted therapy drugs that blck signals needed fr tumurs t grw. Tyrsine kinase inhibitrs may be used with ther anticancer drugs as adjuvant therapy. Tyrsine kinase inhibitrs are used t treat nn-small cell lung cancer and include erltinib and gefitinib. They are types f epidermal grwth factr receptr (EGFR) tyrsine kinase inhibitrs. Criztinib is a type f tyrsine kinase inhibitr that is used t treat nn-small cell lung cancer with certain gene changes. Immuntherapy - The US Fd and Drug Administratin has apprval the anti PD-1 immuntherapy pembrlizumab (Keytruda), in cmbinatin with pemetrexed and carbplatin, fr patients with untreated metastatic nn-squamus nn small-cell lung cancer (NSCLC). The apprval was based n results f a chrt frm KEYNOTE-021, an pen-label, multichrt trial. The study cmpared 4 cycles f pemetrexed and carbplatin in 63 patients vs pemetrexed/carbplatin plus 200 mg pembrlizumab intravenusly every 3 weeks in 60 Octber 2017 Page 15

16 patients until prgressin r unacceptable txicity. Eligible participants had lcally advanced r metastatic nn-squamus NSCLC and had nt previusly received any systemic therapy. Patients in either arm culd als receive pemetrexed as maintenance therapy at the investigatr s discretin. Patients were randmized by PD-L1 tumur expressin (tumur prprtin scre [TPS] < 1% vs TPS 1%). Patients wh received pembrlizumab had imprved verall respnse rates and prgressin-free survival. The verall respnse rate was 55% in patients wh received pembrlizumab plus chemtherapy vs 29% in thse wh received chemtherapy alne (P =.0032). The median prgressin-free survival was 13 mnths with pembrlizumab vs 8.9 mnths fr chemtherapy alne fr a hazard rati f 0.53 (95% CI, ; P =.0205). The verall respnse rate amng patients with TPS < 1% was 57% in the pembrlizumabtreated grup vs 13% in the chemtherapy-alne grup. In patients with TPS 1%, the verall respnse rate was 54% in the pembrlizumab-treated grup vs 38% in the chemtherapy-alne arm Serius adverse events in the pembrlizumab arm ccurred in 41% f patients vs 28% in thse wh nly received chemtherapy. The mst cmmn adverse events f any grade amng patients wh received pembrlizumab were cnstipatin (51%), fatigue (71%), and nausea (68%). Grade 3/4 adverse events included dyspnea and fatigue (3.4% each), and diarrhea, nausea, rash, and vmiting (1.7% each). Ten percent f patients discntinued pembrlizumab due t adverse events, with acute kidney injury (3.4%) as the mst cmmn cause. Pembrlizumab can als cause immune-mediated txicities including clitis, endcrinpathies, hepatitis, nephritis, and pneumnitis. Based n the severity, pembrlizumab shuld be either discntinued r withheld, and patients shuld be given crticsterids if needed. The recmmended dse f pembrlizumab fr NSCLC is 200 mg IV every 3 weeks until prgressin, unacceptable txicity, r fr 2 years in patients withut disease prgressin. Laser therapy - laser therapy is a cancer treatment that uses a laser beam (a narrw beam f intense light) t kill cancer cells. Phtdynamic therapy (PDT) - is a treatment that uses a drug, called a phtsensitiser r phtsensitising agent, and a particular type f light. When phtsensitisers are expsed t a specific wavelength f light, they prduce a frm f xygen that kills nearby cells. Each phtsensitiser is activated by light f a specific wavelength. This wavelength determines hw far the light can travel int the bdy. Thus, dctrs use specific phtsensitisers and wavelengths f light t treat different areas f the bdy with PDT. Phtdynamic therapy causes little damage t healthy tissue. It is used mainly t treat tumurs n r just under the skin r in the lining f internal rgans. When the tumur is in the airways, PDT is given directly t the tumur thrugh an endscpe. Octber 2017 Page 16

17 Crysurgery - crysurgery is a treatment that uses an instrument t freeze and destry abnrmal tissue, such as carcinma in situ. This type f treatment is als called crytherapy. Fr tumurs in the airways, crysurgery is dne thrugh an endscpe. Electrcautery - electrcautery is a treatment that uses a prbe r needle heated by an electric current t destry abnrmal tissue. Fr tumurs in the airways, electrcautery is dne thrugh an endscpe. Watchful waiting - watchful waiting is clsely mnitring a patient s cnditin withut giving any treatment until symptms appear r change. This may be dne in certain rare cases f nn-small cell lung cancer. (Natinal Cancer Institute; Medline Plus; CancerNetwrk). Lwering the Risk fr Lung Cancer Lung cancer preventin is a critical tpic, since lung cancer is the leading cause f cancer deaths in men and wmen wrldwide. It is estimated that the risk fr lung cancer can be lwered in 90% f cases thrugh actin and awareness. Smking accunts fr the majrity f preventable lung cancers, but nn-smkers can take actin t lwer their risk as well. Thse wh have already been diagnsed with lung cancer shuld nt despair. Sme f these measures have been shwn t imprve survival after lung cancer is already present. Smking cessatin - smking is respnsible fr the majrity f lung cancers. Quitting all frms f smking at any time can lwer the risk f develping lung cancer, and appears t be beneficial after a diagnsis f lung cancer as well. Radn expsure - expsure t radn in the hme is the secnd leading cause f lung cancer verall, and the number ne cause in nn-smkers. Radn is an invisible radiactive gas that results frm the nrmal decay f radium in the sil. Secndhand smke - expsure t secnd hand smke increases the risk f lung cancer in nn-smkers tw t three fld. Asbests - wrkplace expsure t asbests increases the risk f lung cancer, and cmbined with smking the risk is expnential. Emplyers shuld have safety recmmendatins fr thse expsed. Chemical and ccupatinal expsures - several chemicals used in industry and arund hmes may increase the risk f lung cancer. Labels n hme prducts such as wd stripper, and Material Safety Data Sheets prvided by emplyers, prvide infrmatin n safe expsure and prper masks t use t limit expsure. Diet and exercise - a healthy diet and mderate physical activity bth play a rle in lwering the risk fr lung cancer. (Abut.Cm Lung Cancer). Octber 2017 Page 17

18 Cmplicatins f Lung Cancer Lung cancer can cause cmplicatins, such as: Shrtness f breath - peple with lung cancer can experience shrtness f breath if cancer grws t blck the majr airways. Lung cancer can als cause fluid t accumulate arund the lungs, making it harder fr the affected lung t expand fully when yu inhale. Cughing up bld - lung cancer can cause bleeding in the airway, which can cause yu t cugh up bld (haemptysis). Smetimes bleeding can becme severe. Treatments are available t cntrl bleeding. Pain - advanced lung cancer that spreads t the lining f a lung r t anther area f the bdy, such as a bne, can cause pain. Tell yur dctr if yu experience pain. Pain may initially be mild and intermittent, but can becme cnstant. Medicatins, radiatin therapy and ther treatments may help make yu mre cmfrtable. Fluid in the chest (pleural effusin) - lung cancer can cause fluid t accumulate in the space that surrunds the affected lung in the chest cavity (pleural space). Pleural effusin can result frm cancer spreading utside the lungs r in reactin t lung cancer inside the lungs. Fluid accumulating in the chest can cause shrtness f breath. Treatments are available t drain the fluid frm yur chest and reduce the risk that pleural effusin will ccur again. Cancer that spreads t ther parts f the bdy (metastasis) - lung cancer ften spreads t ther parts f the bdy - mst cmmnly the brain, bnes, liver and adrenal glands. Cancer that spreads can cause pain, nausea, headaches, r ther signs and symptms depending n what rgan is affected. In sme cases, treatments are available fr islated metastasis, but in mst cases, the gal f treatment fr metastasis is nly t relieve signs and symptms. Death - survival rates fr peple diagnsed with lung cancer are very lw. In mst cases, the disease is fatal. Peple diagnsed at the earliest stages have the greatest chances fr a cure. (May Clinic; WebMD). Abut Clinical Trials Clinical trials are research studies that invlve peple. These studies test new ways t prevent, detect, diagnse, r treat diseases. Peple wh take part in cancer clinical trials have an pprtunity t cntribute t scientists knwledge abut cancer and t help in the develpment f imprved cancer treatments. They als receive state-f-the-art care frm cancer experts. Types f Clinical Trials Cancer clinical trials differ accrding t their primary purpse. They include the fllwing types: Treatment - these trials test the effectiveness f new treatments r new ways f using current treatments in peple wh have cancer. The treatments tested may include new drugs r new cmbinatins f currently used drugs, new surgery r radiatin therapy Octber 2017 Page 18

19 techniques, and vaccines r ther treatments that stimulate a persn s immune system t fight cancer. Cmbinatins f different treatment types may als be tested in these trials. Preventin - these trials test new interventins that may lwer the risk f develping certain types f cancer. Mst cancer preventin trials invlve healthy peple wh have nt had cancer; hwever, they ften nly include peple wh have a higher than average risk f develping a specific type f cancer. Sme cancer preventin trials invlve peple wh have had cancer in the past; these trials test interventins that may help prevent the return (recurrence) f the riginal cancer r reduce the chance f develping a new type f cancer. Screening - these trials test new ways f finding cancer early. When cancer is fund early, it may be easier t treat and there may be a better chance f lng-term survival. Cancer screening trials usually invlve peple wh d nt have any signs r symptms f cancer. Hwever, participatin in these trials is ften limited t peple wh have a higher than average risk f develping a certain type f cancer because they have a family histry f that type f cancer r they have a histry f expsure t cancer-causing substances (e.g., cigarette smke). Diagnstic - these trials study new tests r prcedures that may help identify, r diagnse, cancer mre accurately. Diagnstic trials usually invlve peple wh have sme signs r symptms f cancer. Quality f life r supprtive care - these trials fcus n the cmfrt and quality f life f cancer patients and cancer survivrs. New ways t decrease the number r severity f side effects f cancer r its treatment are ften studied in these trials. Hw a specific type f cancer r its treatment affects a persn s everyday life may als be studied. Where Clinical Trials are Cnducted Cancer clinical trials take place in cities and twns in dctrs ffices, cancer centres and ther medical centres, cmmunity hspitals and clinics. A single trial may take place at ne r tw specialised medical centres nly r at hundreds f ffices, hspitals, and centres. Each clinical trial is managed by a research team that can include dctrs, nurses, research assistants, data analysts, and ther specialists. The research team wrks clsely with ther health prfessinals, including ther dctrs and nurses, labratry technicians, pharmacists, dieticians, and scial wrkers, t prvide medical and supprtive care t peple wh take part in a clinical trial. Research Team The research team clsely mnitrs the health f peple taking part in the clinical trial and gives them specific instructins when necessary. T ensure the reliability f the trial s results, it is imprtant fr the participants t fllw the research team s instructins. The instructins may include keeping lgs r answering questinnaires. The research team may als seek t cntact the participants regularly after the trial ends t get updates n their health. Clinical Trial Prtcl Every clinical trial has a prtcl, r actin plan, that describes what will be dne in the trial, hw the trial will be cnducted, and why each part f the trial is necessary. The prtcl als includes guidelines fr wh can and cannt participate in the trial. These guidelines, called Octber 2017 Page 19

20 eligibility criteria, describe the characteristics that all interested peple must have befre they can take part in the trial. Eligibility criteria can include age, sex, medical histry, and current health status. Eligibility criteria fr cancer treatment trials ften include the type and stage f cancer, as well as the type(s) f cancer treatment already received. Enrlling peple wh have similar characteristics helps ensure that the utcme f a trial is due t the interventin being tested and nt t ther factrs. In this way, eligibility criteria help researchers btain the mst accurate and meaningful results pssible. Natinal and Internatinal Regulatins Natinal and internatinal regulatins and plicies have been develped t help ensure that research invlving peple is cnducted accrding t strict scientific and ethical principles. In these regulatins and plicies, peple wh participate in research are usually referred t as human subjects. Infrmed Cnsent Infrmed cnsent is a prcess thrugh which peple learn the imprtant facts abut a clinical trial t help them decide whether r nt t take part in it, and cntinue t learn new infrmatin abut the trial that helps them decide whether r nt t cntinue participating in it. During the first part f the infrmed cnsent prcess, peple are given detailed infrmatin abut a trial, including infrmatin abut the purpse f the trial, the tests and ther prcedures that will be required, and the pssible benefits and harms f taking part in the trial. Besides talking with a dctr r nurse, ptential trial participants are given a frm, called an infrmed cnsent frm, that prvides infrmatin abut the trial in writing. Peple wh agree t take part in the trial are asked t sign the frm. Hwever, signing this frm des nt mean that a persn must remain in the trial. Anyne can chse t leave a trial at any time either befre it starts r at any time during the trial r during the fllw-up perid. It is imprtant fr peple wh decide t leave a trial t get infrmatin frm the research team abut hw t leave the trial safely. The infrmed cnsent prcess cntinues thrughut a trial. If new benefits, risks, r side effects are discvered during the curse f a trial, the researchers must infrm the participants s they can decide whether r nt they want t cntinue t take part in the trial. In sme cases, participants wh want t cntinue t take part in a trial may be asked t sign a new infrmed cnsent frm. New interventins are ften studied in a stepwise fashin, with each step representing a different phase in the clinical research prcess. The fllwing phases are used fr cancer treatment trials: Phases f a Clinical Trial Phase 0. These trials represent the earliest step in testing new treatments in humans. In a phase 0 trial, a very small dse f a chemical r bilgic agent is given t a small number f peple (apprximately 10-15) t gather preliminary infrmatin abut hw the agent is prcessed by the bdy (pharmackinetics) and hw the agent affects the bdy (pharmacdynamics). Because the agents are given in such small amunts, n infrmatin is btained abut their safety r effectiveness in treating cancer. Phase 0 trials are als Octber 2017 Page 20

21 called micr-dsing studies, explratry Investigatinal New Drug (IND) trials, r early phase I trials. The peple wh take part in these trials usually have advanced disease, and n knwn, effective treatment ptins are available t them. Phase I (als called phase 1). These trials are cnducted mainly t evaluate the safety f chemical r bilgic agents r ther types f interventins (e.g., a new radiatin therapy technique). They help determine the maximum dse that can be given safely (als knwn as the maximum tlerated dse) and whether an interventin causes harmful side effects. Phase I trials enrl small numbers f peple (20 r mre) wh have advanced cancer that cannt be treated effectively with standard (usual) treatments r fr which n standard treatment exists. Althugh evaluating the effectiveness f interventins is nt a primary gal f these trials, dctrs d lk fr evidence that the interventins might be useful as treatments. Phase II (als called phase 2). These trials test the effectiveness f interventins in peple wh have a specific type f cancer r related cancers. They als cntinue t lk at the safety f interventins. Phase II trials usually enrl fewer than 100 peple but may include as many as 300. The peple wh participate in phase II trials may r may nt have been treated previusly with standard therapy fr their type f cancer. If a persn has been treated previusly, their eligibility t participate in a specific trial may depend n the type and amunt f prir treatment they received. Althugh phase II trials can give sme indicatin f whether r nt an interventin wrks, they are almst never designed t shw whether an interventin is better than standard therapy. Phase III (als called phase 3). These trials cmpare the effectiveness f a new interventin, r new use f an existing interventin, with the current standard f care (usual treatment) fr a particular type f cancer. Phase III trials als examine hw the side effects f the new interventin cmpare with thse f the usual treatment. If the new interventin is mre effective than the usual treatment and/r is easier t tlerate, it may becme the new standard f care. Phase III trials usually invlve large grups f peple (100 t several thusand), wh are randmly assigned t ne f tw treatment grups, r trial arms : (1) a cntrl grup, in which everyne in the grup receives usual treatment fr their type f cancer, r 2) an investigatinal r experimental grup, in which everyne in the grup receives the new interventin r new use f an existing interventin. The trial participants are assigned t their individual grups by randm assignment, r randmisatin. Randmisatin helps ensure that the grups have similar characteristics. This balance is necessary s the researchers can have cnfidence that any differences they bserve in hw the tw grups respnd t the treatments they receive are due t the treatments and nt t ther differences between the grups. Randmisatin is usually dne by a cmputer prgram t ensure that human chices d nt influence the assignment t grups. The trial participants cannt request t be in a particular grup, and the researchers cannt influence hw peple are assigned t the grups. Usually, neither the participants nr their dctrs knw what treatment the participants are receiving. Octber 2017 Page 21