Basic Principles of Nutrition in Patients With Cancer
CCSS investigators reported the following independent risk factors for obesity in childhood cancer survivors: Changes in urinary ion excretion and related renal enzyme activities in fluoride-treated rats. Curcumin has been noted to sequester superoxide O 2- radicals with an IC 50 of 5. If you take creatine, it might be good or it might be bad. Journal of Bone and Mineral Research 9
I never over-dose on the stuff, I typically take less than recommended and cycle off of it after two months. So, 2 on and 2 off cycle. Im in the weight room after school every day and I was taking Whey Protein and it worked okay but the Creatine is amazing I have seen an increase in my lifting ,and I dont have to drag myself in the weight room.
It gives me the energy to lift that extra rep, add that extra weight and run that extra mile. I am glad that you put this article up because I was hearing the good and the bad people dieing from Creatine, and I havent had any side effects. I was reading the other reply and would Creatine affect my growth if taken reguarly with hard workouts? It was shown by many researches that creatine not only harmless but also gives results comparable to anabolic steroids, when taken properly.
Different people react differently to supplements like creatine and so the best way to actually measure the damaging side effects of creatine is to see for yourself if any do occur. You can then weigh up whether you should continue or discontinue the usage of creatine for yourself. Never go over the recommended dosages though because then damaging effects probably will occur.
I took creatine and gained 3 stone of mass, was extremely happy with the results until I suffered a massive heart attack. I mamaged to survive it but was told that i have to be on medication all my life and that I will be unable to get an erection again because of the water retention. I have lost my wife due to this. I have also lost my house because of buying so much creatine.
If you are skinny, so what, just go down the pub, have 6 pints and screw an ugly fat bird. Some things never change, even with creatine! I have been taking it for over 6 months now, i am 17 and have gained just over a stone. I am also taking whey. Given me good results only problem i do sumtimes get cramp.
You will see little to no improvement to your body by taking these other supplements. Especially the ones you see behind the locked glass case, they purposely mark up prices to make it look like you are taking something close to steroids that is legal. I say, just take creatine along with a multivitamin or with protein shakes if you wanna bulk up fast. If you are dehydrated and taking creatine other shitty supplements you can have a seizure and nearly die in the ER like one of my Soldiers.
My sister was blinded from the increase in spinal fluid from using creatine. Her workout partner suffered a blown out spine from resuming a workout too soon after injury, again, creatine softened the conncting tissues that held the inside of the spine inside the spine.
Creatine can be very dangerous for some people. This article is dangerous and irresponsible. The only safe creatine is from food sources. I am actually shocked they were dumb enough to say that for being cardiologists. Your just an idiot if you think it did. Im a skinney person looking to bulk up what other supplements along with creatine should i use to help speed up the process. You guys are fucking idiots.
I took creatine for a couple of months and my heart started to hurt alot one week. It hurt whenever i tried to breathe and I had constant chest pains. The doctor I went to diagnosed creatine as the problem. I took creatine about a year ago and it was fine to begin with, but the longer I took it the more aggressive I became especially if I had a few beers as well. I stopped taking it becuase of this. This article seems biast towards people taking it in the way it is written, most of the articles on the internet are to increase the size of the market for people to take it, including probably some of the comments made on the article.
So i have been taking creatin for about 2months. Before takin creatine i was very skinny. If you are serious about getting bigger and looking better then i strongly suggest that YOU take this suppliment! I took creatine for approximately 2 months. The only downsides for me were i had to drink almost twice as much water, some of my previous definition was lost due to bloating, and I would get occasional mood swings with anger. Anyhow I killed a man for staring at my girl.
Now I gotta fight for my life everyday. I joined the Aryan brotherhood and they have access to creatine. But there goes my goodtime. Creatine stole my life! Richard Simmons fuck you too for being such a little punk bitch.
It was watching your faggot ass that made me wanna bulk up and become musclebound. I never felt that way watching Chuck Norris. Oh yeah btw — the things that hurt: Now none of those things hurt since I stopped doing that wicked shit.
But I gotta tell my asshole is killing me. Damn here comes a guard. Lot of impurities in all that Chinese shit which it all is. There is no such thing. Creatine is not going to mess your heart up or cause aggression. Of course Chinese contaminated products have the residule poison from the chemicals used in seperating it from meat sources on top of contaminated meat sources plus god knows what proably lead cause those fuckers have it in everything else.
With that being said, creatine causes increased atp levels which can increase tycardia in cardiac arythmia sensitive individuals. As for aortic complications as stated above there exist no evidence of such. Creatine is the most tested supplement in supplement history. I guess just ignorant kids or foolish adults. Oral creatine supplementation is widely used in sportsmen and women.
Side effects have been postulated, but no thorough investigations have been conducted to support these assertions. It is important to know whether long-term oral creatine supplementation has any detrimental effects on kidney function in healthy population. Creatinine, urea, and plasma albumin clearances have been determined in oral creatine consumers 10 months to 5 yr and in a control group.
There were no statistical differences between the control group and the creatine consumer group for plasma contents and urine excretion rates for creatinine, urea, and albumin. Clearance of these compounds did not differ between the two groups.
Thus, glomerular filtration rate, tubular reabsorption, and glomerular membrane permeability were normal in both groups. Neither short-term, medium-term, nor long-term oral creatine supplements induce detrimental effects on the kidney of healthy individuals. Taking a creatine supplement when weight training is safe all you are doing is topping up what ever you burn off during a training session.
I have been taking Creatine since the s. No real harm till recently. My balls fell off. Flushed them down the toilet by mistake. Now i want to focus on my stomach, i know thats the toughest area to work on.
So my question is would the creatine have any affect on that? A cold dark stare came over my face. I did some creatine and destroyed the place. I fucked em both up. Then I fucked a chicken and a pig too, lost my mind for more than a minute or two. Started barking like a dog while jumping around. Climbed on top of the barn then fell to the ground. Got the screamin shits tried to losen the stress. Stumbled and tripped and rolled in the mess.
Please forgive me grandpappy you goddamn old mummy. You scarred me and fucked me, because I trusted you. Why dont you actually work for it here you work out for like what an hour o man thats tough just bench some curl some do some crunches maybe 2 or maybe even 3 pullups and oo wait pushups and then talk for the rest of the time and thats your workout and your arms get big why would you be so proud of that and look and Rodney o i forget his last names but his arms are bigger than your arms and legs put together they are huge and guesss what he didnt do roids or possibly criatine so get a fricken life and actually try and when your done doin creatine youll probably get fat and youll have to take creatine for the rest of your life if you dont wanna get fat plus you dont know what the long term effects are and i have a six pack and it looks good and i didnt cheat.
Creatine for the rest of your life? Everything you posted is so ignorant and completely stupid you should be beaten. Mostly for comedic value. You have the simple minds of sheep! You low IQ brainwashed fools need to get that in your heads. If I wanna take drugs that make ME stronger look better etc. And we All humans Have normal creatines stored in our muscles. Healthy adults can supply themselves with more creatine in meats And many vegetables. Its great for making you stronger and bulking up, but it also makes you slower, ive noticed a great decrease in my punching speed.
I also know for a fact that sprinters use creatine and show no slow down in cardiac recovery they train just as often with no need in extended rests , so this puts the cardiac muscle recovery issue to question.
I just recently made my purchase of creatine. Just took the first glass. No major side effects that will keep me from taking it. S I plan to take far less than stated in the future next time. Major dobt of People Like me is whether der will b any hormone imbalance……………… looking forward for an answer….
Well I train about 7 days a week, sometimes times a day. I wanted to take take creatine for tje extra energy boost, nut after reading all of this I decided not to. Rather figure out your diet that has to do with carbohydrates and protein intakes, and naturally with patience and determination, I believe we all could have a great journey. Training is not a destination, but rather a journey. People who are goal orientated focus on the means of the end result.
Once one goal is reached, another starts. The old fashioned way without scientifically modified supplements is the purest way to seek great fitness, and pure results, see how much you are determined, and stick to the natural way. I weigh the same as when I was in High School.
Bought a jar of this shit and started eatin fistfulls of it,mixed with everything. Did some sit ups and push ups and gained 10 lbs. Got a big ol zit on my dick, though………….. They must use it to speed up tha muscle growth.
Otherwise they might keep on doing workout for the whole lifetime nang may gain no or very less muscle. Concequently they put the whole blame on gym. Plz use it and then see the positive effects. I am conducting research on the psychological effects of creatine including levels of aggression, attention and memory. A healthy diet that includes 6 small meals a day, eating only lean meat such as chicken, salmon, tuna, beans as well as green vegetables, fruit, etc..
Workout with weights three days a week and do High intensity interval cardio the other three days per week, and you will have the body that you have always desired in no time.
I date a RD registered Dietitian and I can guarantee you that with correct eating and regular exercise that you can get the same results as you can with creatine. Maybe it wont happen quite as fast and in a nation of fast food and inpatients that might be a turn off but correct nutrition is the only way to get in amazing shape with no side effects.
I weight lbs and can bench over lb and run full marathons with a solid 8 min mile pace. Think about the natural way before wasting you money on chemicals. You can get the same nutrients and protein from chickens and fish supplemented with carbs veggies and fruits. I can see the logic in thinking creatine put water in the heart also, however you should never take it for 5 months straight that is far to long of a cycle, I hope your son recovers.
I tried Creatine as part of a weight loss program, thinking it would improve muscular definition. It packed half a stone on me in a week of pure fluid. I was totally deflated when I went to weigh myself after having trained for a solid 2 days and a rest day then 2 days in a week of 4 sessions, to find my weight was up. I laughed when I read about Creatine retaining fluid in the body and quickly stopped taking it. I have lost over a stone of weight, hopefully fat, now that all the fluid has gone out of my body after taking Creatine.
I did notice when I was taking Creatine how I never had to use the loo much even when I was gulping water down at the gym. I too have been taking creatine, with some muscle gain but nothing too exciting. My bench is up to lbs, which I think is pretty good as I am no 70 years old. There is nothing wrong with creatine!!
As long as you take it as directed you will be fine. As for all of the kidney type side effects, that has been proven to be a myth when it comes to creatine itself.
Any kidney issues can be related to other problems during any type of weight lifting. Weight lifting can cause kidney issues by an indirect route.
Strenous weight lifting can damage the muscles. In fact, this is basically how the muscles get bigger. They get damaged a little and heal back stronger. When muscle tissue is damaged a protein called myoglobin is released.
Myoglobin breakdown products can crystalize in the kidneys and damage them. I tried creatine for a few weeks and put on about 3kg of muscle, although i lost it all after stopping. My friend said he got really bad bowel control, and was forced to stop taking it….
I go gym 3 times per week and take a ripped protien and get comments about how much bigger i am getting, i think the key is to stay at it, and eat a balanced diet, after a year or so of dedication you will have awesome gains…. For all the 16 year olds, forget steroids or creatine you dont need it just lift weight, take protien, and change your workout program every 3 months.
The people on this blog are actuall users of this product and are admitting they have had complications, just something to think about. It will not effect every person who takes this product, but you really have to think is it worth risking your health…. If you want to improve the look of your body or get stronger there is natural proven methods that should be considered before taking an untested product, you are not mice. Dont be the test. Also my dad is 70 y.
HI everybody one of my suggestions are to take the new creatine tablets. I take creatine monohydrate, i am on my second cycle and it works pretty well. I have gained a few pounds after a 6 week time, took 6 weeks off, and now i am back on it.
The first few days some stomach problems may occur, but i have not gained any acne or anything like that. I take a tablespoon with 10 oz. I suggest it to anyone trying to get bigger, quick. Any questions, email me at peri5menis aol. All i can say is if u wanna use creatine, do it its a matter of if you want to or not.
Just drink alot of water. Do a cycle take 3 weeks off then do it again youll get massive. Please link me to unbiased studies with conclusive results. Also, did it ever occur to you that creatine may affect each person differently? Let me tell you what has happened to me after taking creatine. Virtually no libido, it vanished. Also, severe gastro intestinal problems ranging from constipation to loose stools. Lastly, becoming extremely fatigued. Just stay away from this stuff. Three years ago i bought creatine and little by little i put it in my cats water ….
Personally, creatine monohydrate had mixed effects with me. Within the first week of using it, I experienced a major decrease in lactic acid build-up, which is the burning sensation you get in your muscles while you are working out, and this was a very positive effect.
I used the regular 5 gram dosage each day, and I drank about bottles of water a day. I loved the pumped feeling in my muscles, but, I hated the bloated look in my mid section. As far as negative side effects, I did notice acne suddenly increasing, and I especially hated frequently urinating in school, along with bad diarrhea. I never had cramps or anger outbursts, and the water weight decreased fairly rapidly when I stopped using it.
I recommend the 5 gram dosage daily instead of the loading phase, because 5 grams was enough to give me diarrhea, imagine what 20 grams would do to you, you would probably flood a stall with diarrhea. Okay, a lot of ppl are saying a lot of stuff, i think u shud also have a luk at this article b4 using this supplement, no matter in wat form!
I have 2 accept that i too got carried away, was lured n made one of my dumbest mistakes, when i bought a very famous creatine product……Now i have stopped usin it n i cant get rif of it either!! I felt that it made me tense n dat messes with ur feelings n all n all this isnt gud 4 sex! My perceptions changed dramatically when i was told by a very nice highly experienced n sizzilin lady, when i was showing off my biceps n askin her to feel how hard they were, she said dat she doesnt care bout my biceps, the only thing that matters to her is my DICK!!
SO, y go crazy….. Took it 8 years ago. I have started takin creatine monohydrate. And i have been sufferin from extreme heart burn from this product. I have stomach alcers, and i think that this product has only made it worse. My weight 2 months ago was 55 kg and now it is 20 kg more i got confidence in myself but now i ve left taking creatine and i m going to gym regularly.
But creatine has side effects too i got pimples on whole of my back. I took creatine when I was 17 for the first time. I only took half of the recommended dosage just to be extra careful and drank plenty of water. Before taking creatine I had no problems whatsoever with my health, besides the fact that I was only about lb and wanted to bulk up. After taking creatine for close to 5 months, unexpectedly I had blood in my urine.
After getting checked by multiple doctors, they all told me to stop taking creatine. I am contemplating taking creatine again but in much smaller amounts because without it I see little to no gains even when I work out routinely. Lost 20 kilos after starting to use ganic-f.
In December i donated a kidney to my brother. WAnt to use ganic-f to maintain weight and fitness. Reading the comments on kidney damage scares me. I need some good advice. Should i stop taking it? But dont take my word for it try it….
Many of the people I work with and work out with have taken creatine forever. Some of these negative claims are absolute BS. Follow the directions on the bottle. Same goes with iron and many other supplements in ridiculous amounts. To ages 17 and under. Im 23 now and had taken creatine off and on for a few years. To the younger kids taking creatine. Its a great tool if your wanting to bulk up because its hard to at that age.
But the potential side effects are not worth it. For most, your metabolisms are fast and its hard to bulk up. Be patient, as you get older your body will naturally fill out, metabolism will slow down, and with hitting the weights you will deff.
Hi dear readers, check it out that i am very experienced person in this field as i myself took lots of lots of supplements like MegaMass SeriousMass Steriods and lot of other things to be looked huge. But please dont take it for any cost. It is useless and harmfull. Life is yours and decision is yours. HI i bought a creatine grams tin iam doing my workouts no any special different between my body. I wonder if there are any side effects if you take it in small daoses ex.
You have to keep your metabolism regulated at a high rate to keep from turning into a marshmallow…. For those who are asking if creatine is ok to take with Hydroxycut……. I took the recommended dosage and exercised regularly. The only noticable side effect was some extra bloating. If you are going to use the product, take it before exercise in the right dosage.
It did give me extra energy. Doses were 5g to 10g. Muscles will flood with water while on it but sets seem easier and generally you fatigue slower.
Four days ago i did my normal dosage then worked out, felt dizzy, sight seemed fuzzy, and had nausea. I ate and tried to take fluids in but I vomited. I was taken to the hospital and received an iv to replenish and get rid of my nausea with zofran. I had blood taken and it was determined that I had acute elevated levels of creatinine. My advice to anyone is not to take more than 10g in a dosage or your kidneys can be stressed. I think cycling should be utilized. Say hello to bloating and goodbye to your six pack.
Your blood flow to your penis will be altered as well , so yes your penis does technically shrink!!! You will have a better looking physique and be so much healthier!
The heart is the most important organ in the body…u lose it your gone. SO its either the muscle or your life…YOU decide…. I am a weightlifter looking to get ready for football next season.
Does anybody recomend me to take creatine? I have been taking creatine for a long time and i always end of getting muscle cramps in my legs …. I have a 14 year old son that is working out with p90x and looking to build muscle mass and put weight on. What would you reccomend. Is there a supplement shake with protein as well as creatine and is it safe for this age? Glad i found this article.
There is a lot of truth in the side effects. In the past i had no issues. Stomach cramps Diaoreah Soft Stools Within 5 mins of taking it, i need to take a dump. The benefits are very good: The appearance of the bulky look is great.
The ability to push more reps is even better. Who wants to die just to get bigger. No side effect will happen if u intake creatine as u needed.. Yes, I have more strength and all, I have been taking creatine for the past 8 months, 5 g a day..
I drink gallons of water a day.. I drink lots of water to cleanse my kidneys, but I have had about 9 lbs of bloat on me, or so..
I think it is.. I honestly feel a bit heavy, im thinking its just the water weight, my mid section looks puffy.. You feel that you are carrying around extra weight on you. I eat healthy, but so far i have noticed the insane amount of bloat..
Its pissing me off just thinking about it now. I will come back in 2 weeks to tell you how it went for me.. Starting today i will stop creatine, then weigh myself and post results. I will continue my routine, but a harder routine..
More cardio to get rid of the crappy ass bloat that i have. I took creatine Gluconate for about 10 months with no problems at all and the results were ok, however. I added beta-alanine to the mix and as expected I got the tingles and also the skin on my head became really red.
I experienced a increased reps and strength! I was pushing just over my expected thresholds! Though, after 9 sessions I started getting headachs that increased in severity that bad that I couldnt train Yes I consumed sufficient volumes of water. I stopped both and after 3 weeks I was fine. The CCSS reported that with decreased cumulative dose and frequency of therapeutic radiation use over treatment decades from to , survivors have experienced a significant decrease in risk of subsequent neoplasms.
However, survivors still frequently experience life-altering morbidity related to effects of cancer treatment on endocrine, reproductive, musculoskeletal, and neurologic function. Late effects also contribute to an excess risk of premature death among long-term survivors of childhood cancer as observed in the following:. Despite high premature morbidity rates, overall mortality has decreased over time.
The former reflects improvements in therapeutic efficacy, and the latter reflects changes in therapy made subsequent to studying the causes of late effects.
The expectation that mortality rates in survivors will continue to exceed those in the general population is based on the long-term sequelae that are likely to increase with attained age. If patients treated on therapeutic protocols are followed up for long periods into adulthood, it will be possible to evaluate the excess lifetime mortality in relation to specific therapeutic interventions.
Little information is available on the conditional probabilities of death among adolescent and young adult cancer patients who survive more than 5 years after their diagnosis. According to this study, most adolescent and young adult cancer patients who survived at least 7 years after diagnosis experienced little difference in survival from that of the general population.
For specific cancer types, including CNS tumors, female breast cancer, Hodgkin lymphoma, and leukemia, evidence of excess mortality risk persisted, or re-emerged, more than 10 years after a cancer diagnosis.
Conditional relative survival was lowest for adolescent and young adult patients with CNS tumors, although patients aged 15 to 29 years demonstrated a higher survival rate than did patients aged 30 to 39 years at the time of diagnosis of their CNS tumors. Recognition of both acute and late modality—specific toxicity has motivated investigations evaluating the pathophysiology and prognostic factors for cancer treatment—related effects. The results of these studies have played an important role in the following areas: The common late effects of pediatric cancer encompass several broad domains, including the following:.
Late sequelae of therapy for childhood cancer can be anticipated based on therapeutic exposures, but the magnitude of risk and the manifestations in an individual patient are influenced by numerous factors. Factors that should be considered in the risk assessment for a given late effect include the following:. A risk-based medical follow-up is recommended, which includes a systematic plan for lifelong screening, surveillance, and prevention that incorporates risk estimates based on the following: Part of long-term follow-up is also focused on appropriate screening of educational and vocational progress.
Specific treatments for childhood cancer, especially those that directly impact nervous system structures, may result in sensory, motor, and neurocognitive deficits that may have adverse consequences on functional status, educational attainment, and future vocational opportunities. These data emphasize the importance of facilitating survivor access to remedial services, which has been demonstrated to have a positive impact on education achievement,[ 36 ] which may in turn enhance vocational opportunities.
In addition to risk-based screening for medical late effects, the impact of health behaviors on cancer-related health risks is also emphasized. Health-promoting behaviors are stressed for survivors of childhood cancer. Targeted educational efforts appear to be worthwhile in the following areas: Proactively addressing unhealthy and risky behaviors is pertinent, as several research investigations confirm that long-term survivors use tobacco and alcohol and have inactive lifestyles at higher rates than is ideal given their increased risk of cardiac, pulmonary, and metabolic late effects.
Most childhood cancer survivors do not receive recommended risk-based care. The CCSS observed the following:. Access to health insurance appears to play an important role in risk-based survivor care. Overall, lack of health insurance remains a significant concern for survivors of childhood cancer because of health issues, unemployment, and other societal factors. Transition of care from the pediatric to adult health care setting is necessary for most childhood cancer survivors in the United States.
When available, multidisciplinary long-term follow-up programs in the pediatric cancer center work collaboratively with community physicians to provide care for childhood cancer survivors. This type of shared care has been proposed as the optimal model to facilitate coordination between the cancer center oncology team and community physician groups providing survivor care. An essential service of long-term follow-up programs is the organization of an individualized survivorship care plan that includes the following:.
For survivors who have not been provided with this information, the COG offers a template that can be used by survivors to organize a personal treatment summary refer to the COG Survivorship Guidelines, Appendix 1. To facilitate survivor and provider access to succinct information to guide risk-based care, COG investigators have organized a compendium of exposure- and risk-based health surveillance recommendations, with the goal of standardizing the care of childhood cancer survivors.
Information concerning late effects is summarized in tables throughout this summary. Several groups have undertaken research to evaluate the yield from risk-based screening as recommended by the COG and other pediatric oncology cooperative groups.
Collectively, these studies demonstrate that screening identifies a substantial proportion of individuals with previously unrecognized, treatment-related health complications of varying degrees of severity. Study results have also identified low-yield evaluations that have encouraged revisions of screening recommendations. Ongoing research is evaluating cost effectiveness of screening in the context of consideration of benefits, risks, and harms. Subsequent neoplasms SNs , which may be benign or malignant, are defined as histologically distinct neoplasms developing at least 2 months after completion of treatment for the primary malignancy.
Childhood cancer survivors have an increased risk of developing SNs that varies according to the following:. SNs are the leading cause of nonrelapse late mortality standardized mortality ratio, This represents a sixfold increased risk of SNs among cancer survivors, compared with the general population. The excess risk of SNs persists even after the age of 40 years. The development of an SN is likely multifactorial in etiology and results from a combination of influences including gene-environment and gene-gene interactions.
Outcome after the diagnosis of an SN is variable, as treatment for some histological subtypes may be compromised if childhood cancer therapy included cumulative doses of agents and modalities at the threshold of tissue tolerance. Unique associations with specific therapeutic exposures have resulted in the classification of SNs into the following two distinct groups:.
Most of the translocations observed in patients exposed to topoisomerase II inhibitors disrupt a breakpoint cluster region between exons 5 and 11 of the band 11q23 and fuse mixed lineage leukemia with a partner gene.
The risk of solid SNs continues to increase with longer follow-up. The risk of solid SNs is highest when the following occur: The histological subtypes of solid SNs encompass a neoplastic spectrum ranging from benign and low-grade malignant lesions e. Solid SNs in childhood cancer survivors most commonly involve the following: With more prolonged follow-up of adult survivors of childhood cancer cohorts, epithelial neoplasms have been observed in the following: Benign and low-grade SNs, including NMSCs and meningiomas, have also been observed with increasing prevalence in survivors who were treated with radiation therapy for childhood cancer.
In addition to radiation exposure, exposure to certain anticancer agents may result in solid SNs. In recipients of a hematopoietic cell transplant conditioned with high-dose busulfan and cyclophosphamide Bu-Cy , the cumulative incidence of new solid cancers appears to be similar regardless of exposure to radiation. In a registry-based, retrospective, cohort study, Bu-Cy conditioning without TBI was associated with higher risks of solid SNs than in the general population.
Chronic graft-versus-host disease increased the risk of SNs, especially those involving the oral cavity. Some well-established solid SNs are described in the following sections. Breast cancer is the most common therapy-related solid SN after HL, largely due to the high dose of chest radiation used to treat HL SIR of subsequent breast cancer, 25— Radiation-induced breast cancer has been reported in one population-based study to have more adverse clinicopathological features, as evidenced by a twofold increased risk of estrogen receptor—negative, progesterone receptor—negative breast cancer observed among year HL survivors, compared with women who had sporadic breast cancer.
Previous studies have also not demonstrated significant difference in overall risk of high-grade versus low-grade tumors. Treatment of childhood Hodgkin lymphoma with higher cumulative doses of alkylating agents and ovarian radiation greater than or equal to 5 Gy exposures predisposing to premature menopause have been correlated with reductions in breast cancer risk, underscoring the potential contribution of hormonal stimulation on breast carcinogenesis.
Most data describing the risk of radiation-associated breast cancer are based on patients treated for HL, with doses ranging from 15 Gy to 50 Gy. Although currently available evidence is insufficient to demonstrate a survival benefit from the initiation of breast cancer surveillance in women treated with radiation therapy to the chest for childhood cancer, interventions to promote detection of small and early-stage tumors may improve prognosis, particularly for those who may have more limited treatment options because of previous exposure to radiation or anthracyclines.
Thyroid cancer is observed after the following: The risk of thyroid cancer has been reported to be fold that of the general population. Refer to the Thyroid nodules section of this summary for information on detecting thyroid nodules and thyroid cancer. Brain tumors develop after cranial irradiation for histologically distinct brain tumors [ 21 ] or for management of disease among ALL or non-Hodgkin lymphoma patients. The risk of subsequent brain tumors demonstrates a linear relationship with radiation dose.
Despite the well-established increased risk of subsequent CNS neoplasms among childhood cancer survivors treated with cranial irradiation, the current literature is insufficient to evaluate the potential harms and benefits of routine screening for these lesions.
Survivors of hereditary retinoblastoma, Ewing sarcoma, and other malignant bone tumors are at a particularly increased risk of developing subsequent bone and soft tissue tumors.
In a population-based study of 69, 5-year survivors of cancer diagnosed before age 20 years, the risk of subsequent primary bone cancer was fold greater than that of the general population, with an estimated year cumulative incidence of 0.
In the same cohort, the risk of subsequent soft tissue sarcoma was almost fold higher than the general population, with an estimated year cumulative incidence of 1. The most commonly observed soft tissue sarcomas were leiomyosarcoma, fibromatous neoplasms, and malignant peripheral nerve sheath tumors. The SIR for subsequent fibromatous primary sarcomas decreased with increasing years from diagnosis and attained age, whereas the SIR for leiomyosarcoma and malignant peripheral nerve sheath tumors remained consistently high across all years from diagnosis and at all attained ages.
Notably, absolute excess risks of all sarcoma subtypes were generally low, except for leiomyosarcoma that followed a retinoblastoma diagnosis absolute excess risks, The risk of developing a leiomyosarcoma was fold higher among survivors of childhood cancer, compared with an excess risk of 0. Retinoblastoma survivors were at the highest risk SIR, Ninety percent of leiomyosarcomas observed after a Wilms tumor diagnosis developed within the irradiated tissue.
Radiation therapy is associated with a linear dose-response relationship. The CCSS reported the following on cases and matched controls in a nested case-control study of 14, childhood cancer survivors: Nonmelanoma skin cancers NMSCs represent one of the most common SNs among childhood cancer survivors and exhibit a strong association with radiation therapy.
These data underscore the importance of counseling survivors about sun protection behaviors to reduce ultraviolet radiation exposure that may exacerbate this risk. Malignant melanoma has also been reported as an SN in childhood cancer survivor cohorts, although at a much lower incidence than NMSCs.
Risk factors for malignant melanoma identified among these studies include the following: Melanomas most frequently developed in survivors of HL, hereditary retinoblastoma, soft tissue sarcoma, and gonadal tumors, but the relatively small number of survivors represented in the relevant studies preclude assessment of melanoma risk among other types of childhood cancer. CCSS investigators observed an approximate 2.
The cumulative incidence of first subsequent melanoma at 35 years from initial cancer diagnosis was 0. Family history of cancer, demographic, or treatment-related factors did not predict risk of melanoma. Among childhood cancer survivor cohorts, lung cancer represents a relatively uncommon SN; the year cumulative incidence of lung cancer among CCSS participants was 0. There is emerging evidence that childhood cancer survivors develop GI malignancies more frequently and at a younger age than the general population.
Collectively, these studies support the need for initiation of colorectal carcinoma surveillance at a young age among survivors receiving high-risk exposures. Consistent with reports among survivors of adult-onset cancer, an increased risk of renal carcinoma has been observed in survivors of childhood cancer.
CCSS investigators reported a significant excess of subsequent renal carcinoma among 14, 5-year survivors in the cohort SIR, 8. Highest risk was observed among the following:. Underlying genetic predisposition may also play a role because rare cases of renal carcinoma have been observed in children with tuberous sclerosis.
Literature clearly supports the role of chemotherapy and radiation therapy in the development of SNs. However, interindividual variability exists, suggesting that genetic variation has a role in susceptibility to genotoxic exposures, or that genetic susceptibility syndrome confers an increased risk of cancer, such as Li-Fraumeni syndrome.
The risk of SNs could potentially be modified by mutations in high-penetrance genes that lead to these serious genetic diseases e. Table 1 summarizes the spectrum of neoplasms, affected genes, and Mendelian mode of inheritance of selected syndromes of inherited cancer predisposition. The interindividual variability in risk of SNs is more likely related to common polymorphisms in low-penetrance genes that regulate the availability of active drug metabolites or are responsible for DNA repair.
Gene-environment interactions may magnify subtle functional differences resulting from genetic variations. The balance between the two sets of enzymes is critical to the cellular response to xenobiotics; for example, high activity of a phase I enzyme and low activity of a phase II enzyme can result in DNA damage.
DNA repair mechanisms protect somatic cells from mutations in tumor suppressor genes and oncogenes that can lead to cancer initiation and progression. Vigilant screening is important for childhood cancer survivors at risk. Well-conducted studies on large populations of childhood cancer survivors have provided compelling evidence linking specific therapeutic exposures and late effects. All pediatric cancer survivor health screening guidelines employ a hybrid approach that is both evidence-based utilizing established associations between therapeutic exposures and late effects to identify high-risk categories and grounded in the collective clinical experience of experts matching the magnitude of the risk with the intensity of the screening recommendations.
The screening recommendations in these guidelines represent a statement of consensus from a panel of experts in the late effects of pediatric cancer treatment.
The COG Guidelines for malignant SNs indicate that certain high-risk populations of childhood cancer survivors merit heightened surveillance because of predisposing host, behavioral, or therapeutic factors. Specific comments about screening for more common radiation-associated SNs are as follows:. Mammography, the most widely accepted screening tool for breast cancer in the general population, may not be the ideal screening tool by itself for radiation-related breast cancers occurring in relatively young women with dense breasts.
On the basis of research among young women with inherited susceptibility to breast cancer, dual-imaging modalities may enhance early detection related to the higher sensitivity of MRI in detecting lesions in premenopausal dense breasts and the superiority of mammography in identifying ductal carcinoma in situ ;[ 91 - 93 ] therefore, the American Cancer Society recommends including adjunct screening with MRI.
Many clinicians are concerned about potential harms related to radiation exposure associated with annual mammography in these young women. In this regard, it is important to consider that the estimated mean breast dose with contemporary standard two-view screening mammograms is about 3. The benefits of detection of early breast cancer lesions in high-risk women must be balanced by the risk predisposed by a 0. To keep young women engaged in breast health surveillance, the COG Guideline recommends the following for females who received a radiation dose of 20 Gy or higher to the mantle, mediastinal, whole lung, and axillary fields:.
The risk of breast cancer in patients who received less than 20 Gy of radiation with potential impact to the breast is of a lower magnitude compared with those who received more than 20 Gy. If a decision is made to screen, the recommendations for women exposed to more than 20 Gy are used.
Cardiovascular disease, after recurrence of the original cancer and development of second primary cancers, has been reported to be the leading cause of premature mortality among long-term childhood cancer survivors. The specific late effects covered in this section include the following:.
The section will also briefly discuss the influence of related conditions such as hypertension, dyslipidemia, and diabetes in relation to these late effects, but not directly review in detail those conditions as a consequence of childhood cancer treatment.
A comprehensive review on long-term cardiovascular toxicity in childhood and young adult survivors of cancer, issued by the American Heart Association, has been published. Overall, there has been a wealth of studies focused on the topic of cardiac events among childhood cancer survivors.
In addition to many smaller studies not covered in detail here, the literature includes very large cohort studies that are either hospital based,[ 6 , 8 - 12 ] clinical trial based,[ 13 , 14 ] or population based,[ 2 , 4 ] many with up to several decades of follow-up.
However, even with decades of follow-up, the average age of these populations may still be relatively young young or middle adulthood. And while the risk of serious cardiovascular outcomes may be very high relative to the age-matched general population, the absolute risk often remains low, limiting the power of many studies. Among the very large studies featuring thousands of survivors, the main limitation has been inadequate ability to clinically ascertain late cardiovascular complications, with a greater reliance on either administrative records e.
While each study design has some inherent biases, the overall literature, based on a combination of self-reported outcomes, clinical ascertainment, and administrative data sources, is robust in concluding that certain cancer-related exposures predispose survivors toward a significantly greater risk of cardiovascular morbidity and mortality.
Although late effects research often lags behind changes in contemporary therapy, many therapies linked to cardiovascular late effects remain in common use today. Using data from four large, well-annotated childhood cancer survivor cohorts CCSS, National Wilms Tumor Study Group, the Netherlands, and SJCRH , a heart failure risk calculator based on readily available demographic and treatment characteristics has been created and validated, which may provide more individualized clinical heart failure risk estimation for 5-year survivors of childhood cancer who have recently completed therapy and up through age 40 years.
One limitation of this estimator is that because of the young age of participants at the time of baseline prediction 5-year survival , information on conventional cardiovascular conditions such as hypertension, dyslipidemia, or diabetes could not be incorporated. In another collaborative study, data from the CCSS, Netherlands, and SJCRH were used to develop risk-prediction models for ischemic heart disease and stroke among 5-year survivors of childhood cancer through 50 years.
Risk scores derived from a standard prediction model that included sex, chemotherapy exposure, and radiation therapy exposure identified statistically distinct low-risk, moderate-risk, and high-risk groups. Chemotherapy in particular, anthracyclines and anthraquinones along with radiation therapy both independently and in combination, increase the risk of cardiovascular disease in survivors of childhood cancer and are considered to be the most important risk factors contributing to premature cardiovascular disease in this population refer to Figure 3.
A, B Marginal Kaplan-Meier and C—E cause-specific competing risk cumulative incidence of cardiac events CEs in childhood cancer survivors stratified according to different treatment groups. Risk factors for anthracycline-related cardiomyopathy include the following: Among these factors, cumulative dose appears to be the most significant refer to Figure 4.
Risk of anthracycline-induced clinical heart failure A-CHF according to cumulative anthracycline dose. Kremer, Clinical heart failure in a cohort of children treated with anthracyclines: A long-term follow-up study, Pages , Copyright , with permission from Elsevier. It remains unclear how best to add together doses of different anthracycline agents. A variety of anthracycline equivalence formulas in relation to doxorubicin have been used; however, they are largely based on hematologic toxicity equivalence, and may not necessarily be the same for cardiac toxicity.
Other agents such as idarubicin, epirubicin, and mitoxantrone an anthraquinone were designed to reduce cardiac toxicity while maintaining similar antitumor effect, although data supporting this are primarily limited to adult cancer patients. Cardioprotective strategies that have been explored include the following:. There are more data for dexrazoxane as a cardioprotectant, but again, mainly in adult cancer patients, for whom it is approved by the U. While anthracyclines directly damage cardiomyocytes, radiation therapy primarily affects the fine vasculature of affected organs.
Late effects of radiation therapy to the heart specifically include the following:. Similar to anthracyclines, manifestation of these late effects may take years, if not decades, to present. Finally, patients who were exposed to both radiation therapy affecting the cardiovascular system and cardiotoxic chemotherapy agents are at even greater risk of late cardiovascular outcomes. Cerebrovascular disease after radiation therapy exposure is another potential late effect for survivors.
As with cardiac outcomes, risk increases with cumulative dose received. Various cancer treatment exposures may also directly or indirectly influence the development of hypertension, diabetes mellitus, and dyslipidemia.
Childhood cancer survivors should be closely screened for the development of these cardiovascular conditions because they represent potentially modifiable targets for intervention. This includes being aware of related conditions such as obesity and various endocrinopathies e.
Some, but not all, studies suggest that female sex may be associated with a greater risk of anthracycline-related cardiomyopathy. While much knowledge has been gained over the past 20 years in better understanding the long-term burden and risk factors for cardiovascular disease among childhood cancer survivors, many areas of inquiry remain, and include the following:.
Various national groups, including the National Institutes of Health—sponsored COG refer to Table 2 , have published recommendations regarding screening and surveillance for cardiovascular and other late effects among childhood cancer survivors.
At this point, there is no clear evidence at least through age 50 years or 30—40 years posttreatment that there is a plateau in risk that occurs after a certain time among survivors exposed to cancer treatments associated with cardiovascular late effects.
However, a growing amount of literature is beginning to establish the yield from these screening studies, which will help inform future guidelines.
Given the growing evidence that conventional cardiovascular conditions such as hypertension, dyslipidemia, and diabetes substantially increase the risk of more serious cardiovascular disease among survivors, clinicians should carefully consider baseline and follow-up screening and treatment of these comorbid conditions that impact cardiovascular health refer to Table 2. There is also emerging evidence that adoption of healthier lifestyle factors may decrease future cardiovascular morbidity in at-risk survivors.
In addition to releasing a comprehensive, publicly available online set of guidelines , the COG has also put together a series of handouts on cardiovascular and related topics, including lifestyle choices written for a lay audience, available on the same website.
Neurocognitive late effects are most commonly observed after treatment of malignancies that require central nervous system CNS —directed therapies. While there is considerable evidence published about this outcome, its quality is often limited by small sample size, cohort selection and participation bias, cross-sectional versus longitudinal evaluations, and variable time of assessment from treatment exposures. CNS-directed therapies include the following:. Children with brain tumors or acute lymphoblastic leukemia ALL are most likely to be affected.
Risk factors for the development of neurocognitive late effects include the following: It should be noted that the cognitive phenotypes observed in childhood survivors of ALL and CNS tumors may differ from traditional developmental disorders. In addition to the direct effects of neurotoxic therapies like cranial radiation, Childhood Cancer Survivor Study CCSS investigators observed that chronic health conditions resulting from non-neurotoxic treatment exposures e.
Survival rates have increased over recent decades for children with brain tumors; however, long-term cognitive effects caused by illness and associated treatments are a well-established morbidity in this group of survivors.
In childhood and adolescent brain tumor survivors, risk factors for adverse neurocognitive effects include the following:. The negative impact of radiation treatment has been characterized by changes in IQ scores, which have been noted to drop about 2 to 5 years after diagnosis; the decline continues 5 to 10 years afterward, although less is known about potential stabilization or further decline of IQ scores several decades after diagnosis. These changes in cognitive functioning may be partially explained by radiation-induced reduction of normal-appearing white matter volume or integrity of white matter pathways, as evaluated through magnetic resonance imaging MRI.
Data are emerging regarding cognitive outcomes after proton radiation to the CNS. Study results demonstrating lack of difference in slopes of IQ change among photon- and proton-treated patients [ 31 ] and significant declines in cognitive processing speed among patients treated with proton radiation [ 32 ] underscore the importance of longitudinal follow-up to determine whether proton radiation provides a clinically meaningful benefit in sparing cognitive function compared with photon radiation.
In addition, studies are beginning to examine cognitive outcomes in histologically distinct subtypes of brain tumors. For example, data from a sample of medulloblastoma patients demonstrated variation in cognitive outcomes by four distinct molecular subgroups and differences in patterns of change over time.
Longitudinal cohort studies have provided insight into the trajectory and predictors of cognitive decline among survivors of CNS tumors. Evidence predictors of cognitive decline among survivors of CNS tumors:. Modeled intelligence quotient IQ scores after conformal radiation therapy CRT by age for pediatric low-grade glioma. Age is measured in years, and time is measured in months after the start of CRT. Conklin, Shengjie Wu, Robert H. Although adverse neurocognitive outcomes observed 5 to 10 years after treatment are presumed to be pervasive, and potentially worsen over time, few empirical data are available regarding the neurocognitive functioning in very long-term survivors of CNS tumors.
The neurocognitive consequences of CNS disease and treatment may have a considerable impact on functional outcomes for brain tumor survivors. The increase in cure rates for children with ALL over the past decades has resulted in greater attention to the neurocognitive morbidity and quality of life of survivors.
The goal of current ALL treatment is to minimize adverse late effects while maintaining high survival rates. To minimize the risk of late sequelae, patients are stratified for treatment according to their risk of relapse. Although low-risk, standard-risk, and most high-risk patients are treated with chemotherapy-only protocols, early reports of neurocognitive late effects for ALL patients were based on heterogeneously treated groups of survivors who received combinations simultaneously or sequentially of intrathecal chemotherapy, radiation therapy, and high-dose chemotherapy, making it difficult to differentiate the impact of the individual treatment components.
However, outcome data are increasingly available regarding the risk of neurocognitive late effects in survivors of childhood ALL treated with chemotherapy only. In survivors of ALL, cranial radiation therapy may result in clinical and radiographic neurologic late sequelae, including the following:. Because of its penetrance into the CNS, systemic methotrexate has been used in a variety of low-dose and high-dose regimens for leukemia CNS prophylaxis.
Systemic methotrexate in high doses with or without radiation therapy can lead to an infrequent but well-described leukoencephalopathy, which has been linked to neurocognitive impairment.
Compared with cranial irradiation, chemotherapy-only CNS-directed treatment produces neurocognitive deficits involving processes of attention, speed of information processing, memory, verbal comprehension, visual-spatial skills, visual-motor functioning, and executive functioning; global intellectual function is typically preserved.
Reduced cognitive status has been observed in association with reduced integrity in neuroanatomical regions essential in memory formation e. However, the long-term impact of these prevalent neurocognitive and neuroimaging abnormalities on functional status in aging adults treated for childhood ALL, particularly those treated with contemporary approaches using chemotherapy alone, remains an active area of research.
Evidence neurocognitive functioning in large pediatric cancer survivor cohorts:. The type of steroid used for ALL systemic treatment may affect cognitive functioning. In a study that involved long-term neurocognitive testing mean follow-up, 9. Intrathecal hydrocortisone also increased risk of attention problems RR, 1. Neurocognitive abnormalities have been reported in other groups of cancer survivors.
Factors such as diagnosis before age 6 years, female sex, cranial radiation therapy, and hearing impediment were associated with impairment. Neurocognitive abnormalities have been reported for the following cancers:. Later studies have yielded mixed results. For example, serial assessment of cognitive and adaptive functioning in a group of survivors younger than 6 years revealed declines in developmental functioning over time. The most pronounced declines were observed in patients with 13q deletion.
Cognitive and academic consequences of stem cell transplantation in children have also been evaluated and include, but are not limited to, the following:. Most neurocognitive late effects after stem cell transplantation are thought to be related to white matter damage in the brain. This was investigated in children with leukemia who were treated with HSCT. In a series of 36 patients, performance on neurocognitive measures typically associated with white matter was compared with performance on measures thought to correlate with gray matter function.
Composite white matter scores were significantly lower than composite gray matter scores, thereby supporting the belief that white matter damage contributes to neurocognitive late effects in this population.
In children with CNS tumors, mass effect, tumor infiltration, and increased intracranial pressure may result in motor or sensory deficits, cerebellar dysfunction, and secondary effects such as seizures and cerebrovascular complications. Numerous reports describe abnormalities of CNS integrity and function, but such studies are typically limited by small sample size, cohort selection and participation bias, cross-sectional ascertainment of outcomes, and variable time of assessment from treatment exposures.
In contrast, relatively few studies comprehensively or systematically ascertain outcomes related to peripheral nervous system function. Neurologic complications that may occur in survivors of childhood cancer include the following:.
Among adult survivors of extracranial solid tumors of childhood median time from diagnosis, 25 years , standardized assessment of neuromuscular function disclosed motor impairment in association with vincristine exposure and sensory impairment in association with cisplatin exposure.
These studies underscore the importance of assessment and referral to rehabilitative services to optimize functional outcomes among long-term survivors. In a cross-sectional study that evaluated neurologic morbidity and quality of life in survivors of childhood ALL median age at evaluation, Female sex, ten doses or more of intrathecal chemotherapy, cranial irradiation, CNS leukemia at diagnosis, and history of ALL relapse were associated with neurologic morbidity.
Neuroimaging studies of irradiated and nonirradiated ALL survivors demonstrate a variety of CNS abnormalities, including leukoencephalopathy, cerebral lacunes, cerebral atrophy, and dystrophic calcifications mineralizing microangiopathy.
The parathyroid glands release a hormone causing calcium to be drawn from the bones to the blood. The high levels of hormones cause the skin on the back, chest, head and limbs to itch. Phosphorous building up in the blood also tends to worsen itching. Constant itching and scratching may also puncture the skin, causing sores and wounds and leaving the patient more susceptible to infection.
Intense itching can be relieved to an extent by removal of parathyroid glands, medication, ultraviolet light therapy and diet. High levels of parathyroid hormone draw calcium from the bones into the blood stream. The mineral imbalance causes the bones to become weak, thin and malformed. Amyloidosis, a condition in which the protein amyloid is deposited in the joints and tendons, is caused by kidney failure. Amyloidosis often results in pain, stiffness and fluid buildup in the joints.
Kidney failure often disrupts the natural circadian system, causing havoc with sleep. People with renal failure often find themselves unable to fall or stay asleep at night. Others may suffer from sleep apnea, affecting their breathing and quality of sleep or from restless leg syndrome, causing restlessness and pain.
Lack of sleep has been found to harm the immune system, leaving the sufferer more susceptible to illness, and may cause exhaustion, depression, weight gain, headaches and in general — impacts the daily quality of life. Treatment includes moderate exercise, adequate nutrition, sleep hygiene counseling and medication.