Cancer Assciatin f Suth Africa (CANSA) Fact Sheet n Wilms Tumur and Other Childhd Kidney Tumurs Intrductin The bdy prduces several kinds f wastes, including sweat, carbn dixide gas, faeces (stl), and urine. These wastes exit the bdy in different ways. Sweat is released thrugh pres in the skin. Water vapur and carbn dixide are exhaled frm the lungs. And undigested fd materials are frmed int faeces in the intestines and excreted frm the bdy as slid waste in bwel mvements. Urine, which is prduced by the kidneys, cntains the by-prducts f metablism - salts, txins, and water - that end up in the bld. The kidneys and urinary tract (which includes the kidneys, ureters, bladder, and urethra) filter and eliminate these waste substances frm the bld. Withut the kidneys, waste prducts and txins wuld sn build up in the bld t dangerus levels. [Picture Credit: Urinary System] In additin t eliminating wastes, the kidneys and urinary tract als regulate many imprtant bdy functins. Fr example, the kidneys mnitr and maintain the bdy's balance f water, ensuring that the tissues receive enugh water t functin prperly and be healthy. When dctrs take a urine sample, the results reveal hw well the kidneys are wrking. Fr example, bld, prtein, r white bld cells in the urine may indicate injury, inflammatin, r infectin f the kidneys, and glucse in the urine may be an indicatin f diabetes. (KidsHealth). December 2017 Page 1
Kidney Cancer Kidney cancer, als knwn as renal cell cancer (RCC), is a disease in which cancer cells frm in the tiny tubes (tubules) r tissues f the kidneys. Kidney cancer generally grws as ne tumur within the kidney, hwever, a kidney may cntain mre than ne tumur, r tumurs may be fund in bth kidneys. Anther frm f kidney cancer is Wilms' tumur, a paediatric cancer that accunts fr 95 percent f childhd kidney cancer cases. Wilms Tumur and ther kidney tumurs are diseases in which malignant (cancer) cells are fund in the kidney. In Wilms tumur ne r mre tumurs may be fund in ne r bth kidneys. Other childhd kidney tumurs, which are diagnsed and treated in different ways, include: Clear cell sarcma f the kidney is a type f kidney tumur that may spread t the lung, bne, brain, and sft tissue Rhabdid tumur f the kidney is a type f kidney cancer that ccurs mstly in infants and yung children. It is ften advanced at the time f diagnsis. Rhabdid tumur f the kidney grws and spreads quickly, ften t the lungs and brain Neurepithelial tumurs f the kidney are rare and usually ccur in yung adults. They grw and spread quickly Desmplastic small rund cell tumur f the kidney is a rare sft tissue sarcma Cystic partially differentiated nephrblastma is a very rare type f Wilms tumur made up f cysts Renal cell carcinma is a rare cancer in children r in adlescents yunger than 15 years f age. Hwever, it is much mre cmmn in adlescents between 15 and 19 years f age. Renal cell carcinmas can spread t the lungs, bnes, liver, and lymph ndes Cngenital mesblastic nephrma is a tumur f the kidney that is usually diagnsed within the first year f life and can usually be cured. One type f cngenital mesblastic nephrma may appear n an ultrasund exam befre birth r may ccur within the first 3 mnths after the child is brn. Cngenital mesblastic nephrma ccurs mre ften in males than females Primary renal synvial sarcma is a rare tumur f the kidney and is mst cmmn in yung adults Anaplastic sarcma f the kidney is a rare tumur that is mst cmmnly fund in children r adlescents yunger than 15 years f age. Anaplastic sarcma f the kidney ften spreads t the lungs, liver, r bnes. There is n standard treatment fr anaplastic sarcma (Natinal Cancer Institute). December 2017 Page 2
Incidence f Childhd Kidney Cancer in Suth Africa The Natinal Cancer Registry (2013) des nt prvide infrmatin regarding the different types f kidney cancer in children under 19 years f age: The frequency f histlgically diagnsed cases f kidney cancer in children under 19 years f age in Suth Africa fr 2013 were as fllws (Natinal Cancer Registry, 2013): Grup - Males 2013 0 4 Years 5 9 Years 10 14 Years 15 19 Years All males 28 7 1 1 Asian males 0 1 0 0 Black males 25 3 1 1 Clured males 2 2 0 0 White males 0 1 0 0 Grup - Females 2013 0 4 Years 5 9 Years 10 14 Years 15 19 Years All females 40 22 3 3 Asian females 1 1 0 0 Black females 2 19 3 3 Clured females 3 1 0 0 White females 3 1 0 0 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. The Suth African experience is that Wilms tumur is the mst cmmn frm f kidney cancer in children and is als knwn as nephrblastma. It has a female predminance and a higher incidence in black children. Seventy eight per cent f children are diagnsed at 1-5 years f age, with a peak incidence at 3-4 years. Wilms tumur usually ccurs spradically, but in 1% f cases it is familial. Cngenital abnrmalities ccur in 12-15% f cases. These include genit-urinary abnrmalities (e.g. hrseshe kidney, hypspadias, undescended testes), cngenital aniridia, WAGR syndrme (aniridia, mental retardatin, genit-urinary abnrmalities), cngenital hemihypertrphy, Beckwith Wiedemann syndrme, and Denys-Drash syndrme (renal disease, pseud-hermaphrditism). Wilms tumur is mstly unilateral, but is bilateral in 5% f cases. An abdminal mass is the mst cmmn presenting sign in 60% f cases. It may be nticed by parents r it may be an incidental finding n examinatin. Hypertensin, which is seen in 25% f patients, is caused by renin prductin by tumur cells. Haematuria may be macrscpic, but is generally micrscpic, and ccurs in 15% f patients. It may lead t irn deficiency anaemia. Rarely Wilms tumur may present with acquired vn Willebrand s disease and a bleeding diathesis, plycythaemia, weight lss, urinary infectin, diarrhea r cnstipatin. (CME). Risk Factrs fr Childhd Kidney Cancer Risk factrs fr kidney cancer include: Smking Obesity High bld pressure December 2017 Page 3
Family histry f kidney cancer Advanced kidney disease and lng-term kidney dialysis Misuse f pain medicatins, including ver-the-cunter medicatins A diet high in red meat r dairy Diabetes kidney cancer risk is arund 40% higher in diabetics cmpared with nndiabetics, metal analyses have shwn. Hwever, excess bdy weight may largely explain this assciatin. Amng diabetics, kidney cancer risk may be higher in insulin users than nn-users, but metfrmin use is nt assciated with increased risk Genetic syndrmes. Kidney cancer is a feature f several genetic syndrmes: Vn Hippel Lindau disease - the risk f smene with vn Hippel Lindau disease develping clear-cell RCC increases with age, reaching 97% by age 60 Hereditary papillary renal cell carcinma (HPRCC) - HPRCC is characterised by ccurrence f type 1 papillary RCC as well as tumurs in ther rgans Hereditary leimymatsis renal cell cancer (HLRCC) - individuals with HLRCC develp benign skin and uterine leimymas and, in sme cases, highly aggressive type-2 papillary RCC Birt-Hgg-Dubé (BHD) syndrme - BHD syndrme is characterised by an increased risk f a number f different types f renal cancer Hrseshe kidney - a hrseshe kidney is an uncmmn birth defect in which the tissue frming the kidneys des nt divide int 2 separate kidneys. Instead, ne large, U-shaped kidney is frmed, usually jined at the bttm. Different types f kidney cancer have been reprted in peple with this defect. [Picture Credit: Hrseshe Kidney] (Dana-Farber Cancer Institute; Cancer Research UKI; Canadian Cancer Sciety; Cancer.Net; Atlas f Genetics and Cytgenetics in Onclgy and Haematlgy). Signs and Symptms f Childhd Kidney Cancer Kidney cancer may nt prduce any nticeable symptms in its early stages. Hwever, as the tumur grws, symptms may begin t appear. Fr that reasn, kidney cancer is ften nt diagnsed until it has begun t spread. Symptms f kidney cancer can include: Bld in the urine (a cnditin called haematuria) A lump r mass in the kidney area Tiredness A general feeling f pr health (malaise) Lss f appetite and/r weight Lw-grade fever Sweats Pain r discmfrt in the side f back f the abdmen (lin pain) Bne pain A general sense f nt feeling well Anaemia (a cnditin that results frm nt having enugh red bld cells) Sme renal cell tumurs prduce abnrmal amunts f certain hrmnes. This can lead t prblems such as: December 2017 Page 4
A high bld calcium level which can cause varius symptms, such as increased thirst, feeling sick, tiredness, and cnstipatin. T many red bld cells being made (plycythaemia). High bld pressure. (Patient.c.uk; University f Califrnia San Francisc Medical Center). Diagnsis f Childhd Kidney Cancer Once a child presents with an abdminal mass, they underg radilgic studies. Mst children have an ultrasund that can determine if the mass riginates frm the kidney and whether it is a slid tumur. Fllwing this, children are evaluated with either a CT scan r an MRI. These studies are dne with the intent f identifying the extent f the tumur and whether it has spread t ther rgans. Wilms' tumur can extend int the vascular system and it is imprtant t identify this preperatively. Wilms' tumur can als ccur in bth kidneys. Abut 5 percent f all patients have bilateral Wilms' tumur at diagnsis. If bilateral tumurs are recgnised n the diagnstic studies, it will change the initial management apprach. It is very imprtant t determine that the kidney is nt invlved with the tumur and is functining nrmally. Other studies are dne t examine the lungs t insure n harmful tumurs are present. The lungs are the mst cmmn site f tumur spread utside f the kidney. A chest X-ray will identify mst abnrmalities, but sme smaller lesins are nly seen n a CT scan. The unfavurable tumur types, such as clear cell sarcma and rhabdid tumur f the kidney, can spread t the bnes. The same is true fr renal cell carcinma. Rhabdid tumur f the kidney can als spread t the brain. Therefre, bne scans and MRIs f the brain are btained in these select patients. The fllwing tests and prcedures may be used: Physical examinatin and histry - an exam f the bdy t check general signs f health, including checking fr signs f disease, such as lumps r anything else that seem unusual. A histry f the patient s health habits and past illnesses and treatments will als be taken Cmplete bld cunt (CBC) - a prcedure in which a sample f bld is drawn and checked fr the fllwing: The number f red bld cells, white bld cells, and platelets The amunt f haemglbin (the prtein that carries xygen) in the red bld cells The prtin f the bld sample made up f red bld cells Bld chemistry studies - a prcedure in which a bld sample is checked t measure the amunts f certain substances released int the bld by rgans and tissues in the bdy. An unusual (higher r lwer than nrmal) amunt f a substance can be a sign f disease in the rgan r tissue that makes it. This test is dne t check hw well the liver and kidneys are wrking Liver functin test - a prcedure in which a bld sample is checked t measure the amunts f certain substances released int the bld by the liver. A higher than nrmal amunt f a substance can be a sign that the liver is nt wrking as it shuld Renal functin test - a prcedure in which bld r urine samples are checked t measure the amunts f certain substances released int the bld r urine by the kidneys. A higher r lwer than nrmal amunt f a substance can be a sign that the kidneys are nt wrking as they shuld December 2017 Page 5
Urinalysis - a test t check the clur f urine and its cntents, such as sugar, prtein, bld, and bacteria Ultrasund exam - a prcedure in which high-energy sund waves (ultrasund) are bunced ff internal tissues r rgans and make eches. The eches frm a picture f bdy tissues called a sngram. An ultrasund f the abdmen is dne t diagnse a kidney tumur CT scan (CAT scan) - a prcedure that makes a series f detailed pictures f areas inside the bdy, such as the chest, abdmen, and pelvis, taken frm different angles. The pictures are made by a cmputer linked t an x-ray machine. A dye may be injected int a vein r swallwed t help the rgans r tissues shw up mre clearly. This prcedure is als called cmputed tmgraphy, cmputerised tmgraphy, r cmputerised axial tmgraphy Abdminal X-ray - an x-ray is taken f the rgans inside the abdmen. An X-ray is a type f energy beam that can g thrugh the bdy and nt film, making a picture f areas inside the bdy Bipsy - the remval f cells r tissues s they can be viewed under a micrscpe by a pathlgist t check fr signs f cancer. Whether a bipsy is dne depends n ne r mre f the fllwing: Cancer is in ne r bth kidneys Imaging tests clearly shw the cancer The patient is n a clinical trial A bipsy may be dne befre treatment, after surgery t remve the tumur, r after chemtherapy t shrink the tumur. (Cancer Research UK; Urlgy Care Fundatin; Natinal Cancer Institute). Staging f Childhd Kidney Cancer The type f tumur fund thrugh pathlgical examinatin is very predictive f the utcme f children with renal tumurs. Fr instance, Wilms' tumurs are separated int favurable and unfavurable types a key distinctin because unfavurable types d nt respnd as well t the standard chemtherapy. The determinatin f tumur type is very imprtant s that the children can receive the apprpriate therapy. [Picture Credit: Staging] As with mst tumurs, a staging system has been develped t stratify patients fr treatment. Patients with tumurs cnfined t the kidney that can be remved cmpletely have the best survival rate. This is mst ntable fr the patients wh have unfavurable micrscpic tissue structure. The tumurs in these patients are nt very respnsive t chemtherapy r radiatin therapy and cmplete remval is essential. December 2017 Page 6
Stage I: Stage II: Stage III: Stage IV: Stage V: Tumur limited t kidney, with cmplete remval Tumur thrugh kidney capsule but cmpletely remved, lcal spillage f tumur, tumur in kidney vein Lcal lymph ndes psitive, diffuse spillage f tumur, psitive surgical margin Metastases t lung, liver, bne, r brain Bilateral tumur The unfavurable micrscpic tissue structure variants f Wilms' tumur fall int three categries: anaplasia, clear cell sarcma, and rhabdid tumur f the kidney. Of the three, nly clear cell sarcma has been respnsive t chemtherapy. Renal cell carcinma that ccurs later in childhd is nt chem-sensitive, much like the adult tumurs. (Urlgy Care Fundatin). Assciated C-Mrbidities The types f secndary cancers include bne and sft tissue sarcmas, breast cancer, lymphma, tumurs f the digestive tract, melanma and acute leukaemias. Certain birth defects and als crrelated with Wilms tumur including Aniridia, hemihypertrphy, cryptrchidism, hypspadias. There are als several syndrmes that are ften assciated with Wilms tumur including Sts syndrme, Perlman syndrme, Simpsn-Glabi-Behmel syndrme, Blm syndrme, Frasier syndrme, Beckwith-Wiedemann Syndrme, Denys - Drash syndrme, and WAGR syndrme. Hypertensin is als a cmmn c-mrbitity assciated with Wilms' tumur. (Physipedia). Aniridia - a cngenital, hereditary, bilateral, extreme frm f iris hypplasia that may be assciated with ther cular defects (Medsape). Hemihypertrphy frmerly called hemihypertrphy, is a rare disrder in which ne side f the bdy grws mre than the ther, causing asymmetry (Healthline). Cryptrchidism Undescended testicle (cryptrchidism) is a testicle that hasn't mved int its prper psitin in the bag f skin hanging belw the penis (scrtum) befre birth. Usually just ne testicle is affected, but abut 10 percent f the time, bth testicles are undescended (May Clinic). Hypspadias Hypspadias is a cnditin in which the pening f the urethra is n the underside f the penis, instead f at the tip. The urethra is the tube thrugh which urine drains frm yur bladder and exits yur bdy (May Clinic). Sts syndrme a genetic cnditin causing physical vergrwth during the first years f life. Children with this syndrme are ften taller, heavier, and have larger heads than their peers (Sts Syndrme Supprt Assciatin). Perlman syndrme is characterized principally by plyhydramnis, nenatal macrsmia, bilateral renal tumurs (hamartmas with r withut nephrblastmatsis), hypertrphy f the islets f Langerhans and facial dysmrphism (Orphanet). December 2017 Page 7
Simpsn-Glabi-Behmel syndrme a cnditin that affects many parts f the bdy and ccurs primarily in males. This cnditin is classified as an vergrwth syndrme, which means that affected infants are cnsiderably larger than nrmal at birth (macrsmia) and cntinue t grw and gain weight at an unusual rate. The ther signs and symptms f Simpsn-Glabi-Behmel syndrme vary widely. The mst severe cases are life-threatening befre birth r in infancy, whereas peple with milder cases ften live int adulthd (Genetics Hme Reference). Blm syndrme an inherited cnditin mst easily nticed by the persn's extremely small stature. Peple with Blm syndrme have chrmsmes which ften break and rearrange. This instability results in high rates f cancer early in life. Sme peple with the disease develp cancerus tumurs befre the age f 10, but mre cmmnly cancer appears beginning in the late teens r early t mid-20s (Cunsyl). Frasier syndrme a cnditin characterized by the presence f an XY sex chrmsme cnstitutin and undermasculinised external genitalia that may range frm ambiguus in appearance t nrmal-lking female genitalia. There is als kidney disease (glmerulsclersis) and gnadal tumurs (gnadblastma). Frasier syndrme is caused by pint mutatins in the WT1 gene (in the intrn 9 dnr splice site) (MedicineNet.cm). Bechwith-Wiedemann syndrme a cngenital (present frm birth) grwth disrder that causes large bdy size, large rgans, and ther symptms MedlinePlus). Denys-Drash syndrme a rare disrder cnsisting f the triad f cngenital nephrpathy, Wilms tumur, and intersex disrders resulting frm mutatins in the Wilms tumur suppressr (WT1) gene (Medscape). WAGR syndrme a rare genetic cnditin that can affect bth bys and girls. Babies brn with WAGR syndrme ften have eye prblems, and are at high risk fr develping certain types f cancer, and mental retardatin. The term "WAGR" stands fr the first letters f the physical and mental prblems assciated with the cnditin: (W)ilms' Tumur, the mst cmmn frm f kidney cancer in children. (A)niridia, sme r cmplete absence f the clured part f the eye, called the iris (singular), r irises/irides (plural). (G)eniturinary prblems, such as testicles that are nt descended r hypspadias (abnrmal lcatin f the pening fr urinatin) in bys, r genital r urinary prblems inside the bdy in girls. Mental (R)etardatin. (Natinal Human Genme Research Institute). Factrs that Affect Prgnsis The prgnsis (chance f recvery) and treatment ptins depend n the fllwing: Hw different the tumur cells are frm nrmal kidney cells The stage f the cancer The type and size f the tumur The age f the child Whether the tumur can be cmpletely remved during surgery Whether the cancer has just been diagnsed r has recurred (cme back) Whether there are any abnrmal chrmsmes r genes December 2017 Page 8
Whether the patient is treated by paediatric experts with experience in treating patients with Wilms tumur and ther kidney tumurs (Cleveland Children s Clinic). Treatment f Childhd Kidney Cancer Surgery - surgery is ften the first treatment a child has fr a kidney tumur. Mst children with Wilms tumur have their kidney with cancer taken ut after the cancer is diagnsed. Smetimes dctrs als remve nearby structures: the adrenal gland (which sits n tp f the kidney), the tube frm the kidney t the bladder (ureter) and the fat arund the kidney. Dctrs may als remve lymph ndes near the kidney. Lymph vessels pick up a watery fluid call lymph frm arund the bdy, filter it thrugh lymph ndes, and return it t the bldstream. Smetimes the lymph system picks up cancer cells traveling in the fluid near a tumur. During surgery, dctrs may check ther sites fr cancer, t, such as the liver and the ther kidney. If they find any tissue that appears t have cancer, they may remve all that tissue r just sme f it fr a bipsy. Smetimes dctrs cannt remve the whle tumur. It may be t large, r the cancer cells may have invaded nearby tissue. Instead, dctrs take a small sample f tumur cells fr a bipsy. Then they ften remve the whle tumur later after they shrink it with chemtherapy. Chemtherapy - chemtherapy means giving medicines that g thrughut yur child's bdy t kill cancer cells. The treating dctrs may suggest chemtherapy t help shrink the kidney tumur r t help kill cancer cells that may be elsewhere in the child's bdy. Children can get these medicines thrugh a vein. These medicines spread arund the bdy thrugh the bldstream. Fr the mst cmmn type f Wilms tumur, dctrs use tw r three chemtherapy medicines. Radiatin - radiatin therapy uses high-energy X-rays t kill cancer cells. A machine sends a dse f radiatin thrugh the uter structures, such as the skin and muscles, int deeper parts f the bdy. The rays are directed at the place where dctrs knw r suspect cancer remains. Dctrs mst ften use this fr patients with stage III r stage IV Wilms tumur. Mst times, dctrs give radiatin fr kidney tumurs after surgery and befre chemtherapy. Radiatin can cause unpleasant side effects, such as nausea, sre thrat r mild skin burning, r lng-term prblems, such as infertility r secnd cancers. Radiatin als can affect the way a child develps. Researchers are lking fr ways t give it in smaller dses r t smaller areas r t use ther treatments instead. (Seattle Children s Hspital). December 2017 Page 9
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 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, December 2017 Page 10
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 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. December 2017 Page 11
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 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. December 2017 Page 12
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. Peple wh participate in phase III trials may r may nt have been treated previusly. If they have been treated previusly, their eligibility t participate in a specific trial may depend n the type and the amunt f prir treatment they received. In mst cases, an interventin will mve int phase III testing nly after it has shwn prmise in phase I and phase II trials. Phase IV (als called phase 4). These trials further evaluate the effectiveness and lng-term safety f drugs r ther interventins. They usually take place after a drug r interventin has been apprved by the medicine regulatry ffice fr standard use. Several hundred t several thusand peple may take part in a phase IV trial. These trials are als knwn as pst-marketing surveillance trials. They are generally spnsred by drug cmpanies. Smetimes clinical trial phases may be cmbined (e.g., phase I/II r phase II/III trials) t minimize the risks t participants and/r t allw faster develpment f a new interventin. Althugh treatment trials are always assigned a phase, ther clinical trials (e.g., screening, preventin, diagnstic, and quality-f-life trials) may nt be labelled this way. Use f Placebs The use f placebs as cmparisn r cntrl interventins in cancer treatment trials is rare. If a placeb is used by itself, it is because n standard treatment exists. In this case, a trial wuld cmpare the effects f a new treatment with the effects f a placeb. Mre ften, hwever, placebs are given alng with a standard treatment. Fr example, a trial might cmpare the effects f a standard treatment plus a new treatment with the effects f the same standard treatment plus a placeb. Pssible benefits f taking part in a clinical trial The benefits f participating in a clinical trial include the fllwing: Trial participants have access t prmising new interventins that are generally nt available utside f a clinical trial. December 2017 Page 13
The interventin being studied may be mre effective than standard therapy. If it is mre effective, trial participants may be the first t benefit frm it. Trial participants receive regular and careful medical attentin frm a research team that includes dctrs, nurses, and ther health prfessinals. The results f the trial may help ther peple wh need cancer treatment in the future. Trial participants are helping scientists learn mre abut cancer (e.g., hw it grws, hw it acts, and what influences its grwth and spread). Ptential harms assciated with taking part in a clinical trial The ptential harms f participating in a clinical trial include the fllwing: The new interventin being studied may nt be better than standard therapy, r it may have harmful side effects that dctrs d nt expect r that are wrse than thse assciated with standard therapy. Trial participants may be required t make mre visits t the dctr than they wuld if they were nt in a clinical trial and/r may need t travel farther fr thse visits. Crrelative research studies, and hw they are related t clinical trials In additin t answering questins abut the effectiveness f new interventins, clinical trials prvide the pprtunity fr additinal research. These additinal research studies, called crrelative r ancillary studies, may use bld, tumur, r ther tissue specimens (als knwn as bispecimens ) btained frm trial participants befre, during, r after treatment. Fr example, the mlecular characteristics f tumur specimens cllected during a trial might be analysed t see if there is a relatinship between the presence f a certain gene mutatin r the amunt f a specific prtein and hw trial participants respnded t the treatment they received. Infrmatin btained frm these types f studies culd lead t mre accurate predictins abut hw individual patients will respnd t certain cancer treatments, imprved ways f finding cancer earlier, new methds f identifying peple wh have an increased risk f cancer, and new appraches t try t prevent cancer. Clinical trial participants must give their permissin befre bispecimens btained frm them can be used fr research purpses. When a clinical trial is ver After a clinical trial is cmpleted, the researchers lk carefully at the data cllected during the trial t understand the meaning f the findings and t plan further research. After a phase I r phase II trial, the researchers decide whether r nt t mve n t the next phase r stp testing the interventin because it was nt safe r effective. When a phase III trial is cmpleted, the researchers analyse the data t determine whether the results have medical imprtance and, if s, whether the tested interventin culd becme the new standard f care. The results f clinical trials are ften published in peer-reviewed scientific jurnals. Peer review is a prcess by which cancer research experts nt assciated with a trial review the study reprt befre it is published t make sure that the data are sund, the data analysis was perfrmed crrectly, and the cnclusins are apprpriate. If the results are particularly imprtant, they may be reprted by the media and discussed at a scientific meeting and by December 2017 Page 14
patient advcacy grups befre they are published in a jurnal. Once a new interventin has prven safe and effective in a clinical trial, it may becme a new standard f care. (Natinal Cancer Institute). Medical Disclaimer This Fact Sheet is intended t prvide general infrmatin nly and, as such, shuld nt be cnsidered as a substitute fr advice, medically r therwise, cvering any specific situatin. Users shuld seek apprpriate advice befre taking r refraining frm taking any actin in reliance n any infrmatin cntained in this Fact Sheet. S far as permissible by law, the Cancer Assciatin f Suth Africa (CANSA) des nt accept any liability t any persn (r his/her dependants/estate/heirs) relating t the use f any infrmatin cntained in this Fact Sheet. Whilst CANSA has taken every precautin in cmpiling this Fact Sheet, neither it, nr any cntributr(s) t this Fact Sheet can be held respnsible fr any actin (r the lack theref) taken by any persn r rganisatin wherever they shall be based, as a result, direct r therwise, f infrmatin cntained in, r accessed thrugh, this Fact Sheet. December 2017 Page 15
Surces and References Atlas f Genetics and Cytgenetics in Onclgy and Haematlgy http://atlasgeneticsnclgy.rg/kprnes/vhlkpr10010.html Canadian Cancer Sciety http://www.cancer.ca/en/cancer-infrmatin/cancertype/kidney/risks/?regin=n#hrseshe_kidney Cancer.Net http://www.cancer.net/cancer-types/kidney-cancer/risk-factrs-and-preventin Cancer Research UK http://www.cancerresearchuk.rg/cancer-inf/cancerstats/types/kidney/riskfactrs/kidneycancer-risk-factrs http://www.cancerresearchuk.rg/cancer-help/abut-cancer/cancer-questins/wilms-tumur Cleveland Children s Clinic http://my.clevelandclinic.rg/childrens-hspital/health-inf/diseases-cnditins/cancer/hicwilms-tumr-and-ther-childhd-kidney-tumrs.aspx CME Ple, J.E. 2010. Wilms Tumur (Nephrblastma). CME 28(7):324-326, July. Cunsyl https://www.cunsyl.cm/services/family-prep-screen/diseases/blm-syndrme/ Dana-Farber Cancer Institute http://www.dana-farber.rg/adult-care/treatment-and-supprt/kidney-cancer/abut- Kidney-Cancer.aspx Genetics Hme Reference http://ghr.nlm.nih.gv/cnditin/simpsn-glabi-behmel-syndrme Healthline http://www.healthline.cm/health/hemihypertrphy-hemihyperplasia#overview1 KidsHealth http://kidshealth.rg/parent/general/bdy_basics/kidneys_urinary.html May Clinic http://www.mayclinic.rg/diseases-cnditins/undescended-testicle/basics/definitin/cn- 20037877 http://www.mayclinic.rg/diseases-cnditins/hypspadias/basics/definitin/cn-20031354 MedicineNet.cm http://www.medterms.cm/script/main/art.asp?articlekey=26380 MedlinePlus http://www.nlm.nih.gv/medlineplus/ency/article/001186.htm December 2017 Page 16
Medscape http://emedicine.medscape.cm/article/1208379-verview http://emedicine.medscape.cm/article/943103-verview Natinal Cancer Institute http://www.cancer.gv/cancertpics/pdq/treatment/wilms/patient/page1 http://www.cancer.gv/cancertpics/pdq/treatment/wilms/patient/page1#keypint5 http://www.cancer.gv/clinicaltrials/learningabut/what-are-clinical-trials Natinal Human Genme Research Institute http://www.genme.gv/26023527 Orphanet http://www.rpha.net/cnsr/cgibin/disease_search.php?lng=en&data_id=3474&disease(s)/grup%20f%20diseases=perl man-syndrme&title=perlman-syndrme&search=disease_search_simple Patient.c.uk http://www.patient.c.uk/health/kidney-cancer Physipedia http://www.physi-pedia.cm/wilms_tumr Seattle Children s Hspital http://www.seattlechildrens.rg/medical-cnditins/cancer-tumrs/kidney-tumrs-treatment/ Sts Syndrme Supprt Assciatin http://stssyndrme.rg/ Staging https://www.ggle.c.za/search?q=childhd+cancer+wilms&surce=lnms&tbm=isch&sa= X&ei=lhOkU7KKEaje7Ab6jDgCQ&ved=0CAYQ_AUAQ&biw=1517&bih=714&dpr=0.9#facr c=_&imgdii=_&imgrc=keqbjexkcunom%253a%3bzdejkfn9texypm%3bhttp%253a%25 2F%252Fwww.physi-pedia.cm%252Fimages%252F8%252F8d%252FWilmstumr.jpg%3Bhttp%253A%252F%252Fwww.physipedia.cm%252FWilms_Tumr%3B600%3B560 University f Califrnia San Francisc Medical Center http://www.ucsfhealth.rg/cnditins/kidney_cancer/signs_and_symptms.html Urinary System http://www.dana-farber.rg/adult-care/treatment-and-supprt/kidney-cancer/abut- Kidney-Cancer.aspx Urlgy Care Fundatin http://www.urlgyhealth.rg/urlgy/index.cfm?article=25 December 2017 Page 17