The risk for bladder and urinary tract toxicities is higher if you got cyclophosphamide (at doses > 8g/m2), ifosfamide, and/or radiation to the abdomen or pelvis. Late effects to the urinary tract can include hemorrhagic cystitis (bleeding inside the bladder) and scar tissue in the bladder (causing you to be able to hold less urine). Symptoms of hemorrhagic cystitis are urinary frequency (going often) and urgency (needing to go right away), blood in the urine, and pain when urinating. Bladder scar tissue can cause difficulty urinating, frequency (going often), or urgency (needing to go right away). There is also a small risk for bladder cancer after treatment with cyclophosphamide, ifosfamide, or radiation to the abdomen or pelvis. If you have any of these symptoms, you should report them to your healthcare provider right away. Alcohol use and smoking can also cause problems with bladder function, so these should be avoided.

Cyclophosphamide can lead to the development of bladder cancer. Your risk is higher if you also got radiation therapy to the abdomen or pelvis. Symptoms of bladder cancer include blood in the urine, urinary frequency (going often) and urgency (needing to go right away), urinating at night, and incontinence (unable to hold your urine). Tell your healthcare provider if you have any of these symptoms. Alcohol use and smoking can also lead to bladder cancer, so these should be avoided.

Peripheral neuropathy is caused by irritation or damage to nerves, leading to feelings of numbness, “pins and needles,” tingling, burning, or a feeling of weakness or heaviness in the arms or legs. Neuropathy can cause trouble with fine motor skills such as buttoning a shirt, sensation of hot or cold (causing a safety hazard), or difficulty walking. For some people, neuropathy goes away within weeks to months after ending therapy or stopping the medication that caused the problem. For others, neuropathy becomes chronic, and you may need physical and occupational therapy, medications, and changes in your environment to keep you safe.

Medications that are not typically thought of as pain medications are often used to manage the pain caused by neuropathy. These could be tricyclic antidepressants, gabapentin and pregabalin. If the pain is not well managed, seeing a pain specialist or physical/occupational therapist may be helpful.

Neuropathy does not typically develop as a late effect, so if you have symptoms suggestive of neuropathy months to years after therapy, other causes should be considered.

Osteoporosis is a decrease in bone density (thinning of the bones) that can lead to fractures (broken bones). The risk for osteoporosis is increased for:

• People who take corticosteroids for more than 2 months (dexamethasone or prednisone, more than 5mg per day).
• People who receive radiation to weight-bearing bones (spine, hips, legs).
• Women who develop premature menopause or have their ovaries removed before menopause.
• Women who take aromatase inhibitors (anastrozole, letrozole, and exemestane).
• Pre-menopausal women who take tamoxifen.
• Men who receive hormone therapy for prostate cancer or have a testicle(s) removed (orchiectomy).
• People who had a gastrectomy (removal of the stomach).
• Several types of chemotherapy have been found to contribute to bone loss, including Cytoxan, cisplatin, carboplatin, ifosfamide, doxorubicin, methotrexate, and possibly imatinib.
• General factors that increase the risk of osteoporosis include: being over the age of 50, smoking, drinking too much alcohol, not exercising, and some chronic health conditions.

There are things you can do to lower your risk of a fracture and strengthen your bones:

• Get 1000-1200mg a day of calcium.
  • It is best to get calcium in a balanced diet, including 4-8 servings of calcium-rich foods a day. Examples of calcium-rich foods are low-fat milk, yogurt, cheese, green leafy vegetables, nuts, seeds, beans, legumes, and calcium-fortified foods and juices.
  • A dietician can provide more guidance in choosing calcium-rich foods. A good resource is www.myplate.gov.
  • If you cannot get the recommended amount of calcium in foods, take calcium citrate supplements. Your body does not absorb calcium supplements well, so spread the dose out by taking 1 tablet several times a day, instead of all at once. If you take Synthroid/ Levothyroxine (thyroid hormone), separate it from calcium doses by at least 4 hours.
• Take 800-1000 IU of vitamin D-3 daily.
  • Your healthcare provider may check blood levels of vitamin D with the 25-OH Vitamin D blood test.
  • Do not take more than 2000 IU of vitamin D3 a day, unless directed by your healthcare provider.
• Weight-bearing exercise and strength training can improve your bone strength.
  • Before you start an exercise program, check with your care team to determine if it is safe.
  • Start with what is comfortable for you and work up to the following recommendations:
    • Get 30-40 minutes of weight-bearing exercise 3 times a week. Weight-bearing exercises are those in which your feet or legs bear your body’s weight while the bones and muscles work against gravity. Examples include walking, jogging, Tai Chi, yoga, and dancing.
    • Strength training 2-3 times per week, with a day of rest in between each session. Complete 8-12 repetitions of exercises like leg extensions, calf raises, leg curls, chest press, latissimus pulldown, overhead press, row machine, and curl-ups, and repeat them two times (2 sets). Choose a weight where the tenth repetition is hard for you to complete, and you can’t complete an 11^th . Now remove 1-5 pounds from that "maximum weight," and use that as your training weight. When you can easily do 12 repetitions, try to increase the weight by 3-5lbs.
  • Your provider can refer you to a physical therapist or a physical medicine and rehabilitation physician for more guidance regarding bone-strengthening exercises.
• Decrease or stop caffeine intake and limit alcohol intake, as these can weaken bones.
• Quit smoking. Learn more about how to get started on OncoLink.
• Your provider may order a DEXA scan, which is a test used to measure the thickness (density) of your bones.

Raynaud's phenomenon is a condition that causes blood vessels in certain areas of the body to constrict or spasm, causing numbness and cold feeling in that area. This may happen when the area is exposed to cold or can be triggered by stress. Most people have symptoms in their hands/fingers or feet/toes, but it can be in the nose, earlobes, lips, or cheeks. Spasm and constriction of the blood vessels leads to decreased blood flow to that area, resulting in a lack of oxygen, causing tissues to appear pale or blue in color. Once the attack is over, the tissues may appear red from the rush of blood back into them.

Survivors who have gotten vincristine, vinblastine, or vinorelbine are at the highest risk for having this issue. Symptoms can start during, or months after treatments are completed. For some people, the symptoms will go away over time, but for others they do not. In some cases, Raynaud's is seen along with hypertension or erectile dysfunction in men because those can also be caused by spasm of the blood vessels.

You should avoid exposing the affected area to cold as this can trigger an attack. Wear gloves if going out in the cold and your hands are affected. Nicotine can also constrict blood vessels, so smoking or vaping should be avoided. Some medications can cause constriction of the blood vessels, including pseudoephedrine, birth control pills, and certain heart and blood pressure medications. Talk to your healthcare provider if you are taking any of these medications and are experiencing Raynaud's phenomenon. Medications that dilate blood vessels may be used to control symptoms in severe cases, but these have their own side effects. You should also have your blood pressure checked every year.

Some cancer medicines can cause your skin or nails to darken all over, or in spots. The change in skin color tends to fade over time but can be permanent. Many people will have very dry or scaly skin while on cancer treatment. Use a mild soap and a hydrating lotion regularly.

Your nails may become weak and brittle. Keep your nails trimmed to avoid them ripping. Do not use fake nails or gel manicures as these can further damage your nails. Taking care of your skin and nails can help them recover. Protect your skin from the sun with SPF >30, protective clothing, and avoid the sun during peak hours (10am-3pm).

Many survivors who have previously had or are currently undergoing chemotherapy report cognitive changes. These changes include difficulty with short term memory, multi-tasking, new learning, reading comprehension, working with numbers, and a decrease in the ability to concentrate. Studies have found that cognitive ability can improve over time in some survivors, but deficits are still present in many long-term survivors, years after treatment.

It is important to remember that some very treatable problems can result in cognitive difficulties, such as thyroid dysfunction, depression, and anxiety, so it is important to check for these problems and treat them. Hypothyroidism (low thyroid hormone levels) is a common issue for survivors and can make you feel "fuzzy" or "out of it." This is easily treatable by taking a thyroid hormone medication. Survivors who are depressed or are experiencing anxiety would benefit from seeing a psychiatrist, psychologist, or other mental health professional experienced in working with cancer patients or survivors.

Some medications are being studied as potential treatments for cognitive changes, but there is not yet enough data to support their use. Some of the things being studied are methylphenidate (Ritalin), modafinil (a medication approved to treat narcolepsy), various antidepressants, herbal therapies (such as ginkgo biloba, ginseng, and certain amino acids). Neurocognitive testing and cognitive rehabilitation may be helpful. Cognitive rehabilitation programs that use exercise, tasks that use memory, and puzzles to "rehabilitate" one's mind may also be helpful. These programs are used for people with brain injuries, but therapists have tailored programs for cancer survivors. Bookstores and websites offer memory training, which may be helpful to survivors. Puzzles using numbers, like Sudoku, may help "exercise" your brain. Fatigue can make cognitive problems worse, so be sure to get enough sleep, get regular exercise, and eat a healthy diet to combat fatigue.

Fertility (or the ability to have children) after cancer therapy is a very complex topic. It is related to the doses and types of medications you got, radiation and/or surgery that may have affected reproductive organs, and your age at the time of treatment. With all of these things, it is sometimes hard to predict a survivor's reproductive health. Regardless of what treatment you got, all survivors should use protection when sexually active if pregnancy is not desired, and to protect against sexually transmitted infections. Survivors who want to know if they can get pregnant should see a reproductive specialist who has experience working with cancer survivors. Specialists can do tests to evaluate fertility.

Chemotherapy meds that most often cause infertility are alkylating agents (including cyclophosphamide, cisplatin, carboplatin, melphalan, and ifosfamide), and the risk is higher with higher doses of these medications. High dose chemotherapy, used in preparation for stem cell/bone marrow transplant, almost always cause the ovaries to stop working and in turn, infertility. Radiation to the abdomen, pelvis, brain, or full body (TBI) can also impact fertility.

Even if you have normal periods after cancer therapy you should be aware that you might still have earlier than expected menopause, which can affect family planning. When pregnancy does occur, you may need to be followed by a "high-risk" obstetrician depending on what treatments you had, and planning for this may be important.

A secondary cancer is one that develops as a result of cancer treatment for another cancer. This is quite rare, but you should be aware of the risk.

Certain chemotherapy medications can cause damage to the blood cells in the bone marrow. In rare cases, this damage can cause leukemia or myelodysplasia (MDS) to develop years after therapy has been completed. Both diseases cause an abnormal production of poorly functioning blood cells, making it difficult for the body to fight infection, carry oxygen to the tissues and prevent bleeding. Because these conditions develop as a result of chemotherapy or radiation exposure, they are often more difficult to treat than typical leukemia or MDS. Leukemia and MDS caused by chemotherapy or radiation therapy typically occurs between 4-10 years after treatment, but can occur even later. One exception is those caused by etoposide (VP-16) or teniposide (two types of chemotherapy), which generally occur within 1-3 years after therapy. Secondary lymphomas have also been seen in Hodgkin's disease survivors who received the MOPP (nitrogen mustard, vincristine, procarbazine, and prednisone) chemotherapy regimen. The medication bendamustine has been linked to secondary lung cancers.

Most chemotherapy medications have been studied extensively, and their side effect risks are well-understood. Research is continuing, however, and new information may become available. You should periodically talk to your healthcare team about new information that becomes available for cancer survivors.

In addition, there have been many new therapies in recent years, including many biologic therapies, monoclonal antibodies, and targeted therapies. We may not know the long-term effects of these medications for many years. As a survivor, you should be an active participant in your healthcare and keep an ear out for new information.

You can revisit Smart ALACC to create an updated plan periodically and visit the Children's Oncology Group Long Term Follow-Up website to learn about any new information.