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Late and Long-term Effects of Cancer and Its Therapy
Ernest H. Rosenbaum, MD, Patricia Fobair, LMSW, MPh, and David Spiegel, MD

Cancer Therapy Possible Latent Side-Effects
Short and Long-Term Psychological Effects

Cancer Therapy Possible Latent Side-Effects
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Knowledge of the possible latent side effects of cancer therapy can arm survivors with knowledge and a plan. By providing and promoting lifestyle interventions it is possible to reduce the rate of current and late comorbidities and adverse therapy related toxic side effects.

Late effects
of therapy involve unrecognized toxicities that occur many years post-therapy.

With the current five-year survival rate of over 64%, the majority of cancer patients will live years and decades longer. At the same time, they face various challenges following potential curative or remission therapy, affecting personality, emotions, and social relations. There are also possible physical changes due to surgery, radiation therapy, chemotherapy and immunotherapy causing physical limitations and challenges to quality of life. Often, there may be changes five or ten years after treatment from delayed side effects, such as heart problems following Adriamycin, Epirubicin or Herceptin therapy. Research is ongoing to evaluate better and safer treatments and also ways of coping and reducing these side effects. In addition, lifestyle changes for improved health have been recommended, as most cancer patients die of other comorbidities usually related to age, such as complications involving heart, lung, kidney, gastrointestinal, or liver problems.

Those who have had amputations, disfiguring surgery, or colostomies, for example, have limitations on daily living activities, self-esteem, and coping, or may suffer from depression. Often, long-term complications from toxic side effects of therapy not only bring back fears and physical problems, but also may require specialized treatments and care to help improve and ameliorate these symptoms.

For example, patients who receive brain radiation therapy may have both short and long-term memory problems, often referred to as chemobrain. Knowing that this could happen can help reduce the anxiety created. After appropriate evaluation, the patient needs to know that this is not a recurrence of the cancer but a delayed side effect. Another example is thyroid failure (hypothyroidism) following neck radiation which included the thyroid gland.

Long-term effects
are side effects or complications of therapy that persist when therapy is completed, requiring patients to develop compensatory treatment programs to relieve or control these side effects. This is in contrast to late effects, which occur months or years post-treatment.

Surgery, radiation, or chemotherapy can cause damage to vital organs, such as heart, lungs, kidneys, and the gastrointestinal tract. Older persons over 65 and 70 may have pre-existing heart, lung, kidney, gastrointestinal, or liver problems, which can be accentuated with anti-cancer therapy, as these organs may be more susceptible to side effects from treatment. 

Peripheral neuropathy, for example, pain, numbness, tingling, loss of sensation or heat/cold sensitivity in extremities or body, is often a side effect for patients receiving Taxol, Taxotere, platinum, vincristine, velban. navelbine and oxaliplatin drugs.

Cardiac dysfunction problems can occur early or late with treatment of Anthracycline drugs, such as doxorubicin (Adriamycin), daunomycin, epirubicin and mitoxantrone. Long-term follow up is recommended for possible congestive heart failure up to twenty plus years and more after treatment. For those who already have cardiac problems, radiation to the heart and treatment with these drugs can also cause progressive cardiac problems. Protective drugs are being developed to delay or prevent damage. In addition, lifestyle changes of diet and exercise are important for promoting better health and disease prevention.

Platinum compounds can cause decrease in kidney function, and this can also be accentuated when there is abdominal radiation involving the kidneys. Platinum compounds can also cause high frequency hearing loss. For those receiving head radiation therapy, cataracts, dry eyes, and dry mouth are common problems. Abdominal radiation can cause chronic diarrhea, malabsorption, milk/lactose intolerance, bowel dysfunction, and weight loss.

Recurrent and Second Tumors
Survivors also need to be followed for many years for the possibility of developing another cancer or a recurrence. It's been estimated that up to 20-25% of patients may face these problems, which could be bone marrow failure, myelodysplasia (dysfunctional bone marrow), or a new cancer. Lifestyle practices can be helpful in reducing the risk of comorbid conditions and possibly second cancers or delayed recurrences.

Fertility Problems
Infertility is a serious concern for patients wishing to have children.

Infertility can occur with patients receiving radiation to the testes, but it is of note that hormone levels in irradiated children usually remain normal as they go through puberty. Radiation to the abdomen and chemotherapy may also affect the reproductive organs (ovaries or testes), resulting in infertility. Thus, ovarian egg cell preservation and sperm banking for future fertilization or in vitro fertilization is necessary for those wishing to have children.

Chemotherapy can cause infertility, but not all drugs have this effect. The alkalating agents, Nitrogen mustard, cyclophosphamide, leukeran, and ifosfamide have been implicated, but a lot depends on the dose and administration.

Loss of ovarian or testicular function may contribute to osteoporosis by decreasing hormone levels (estrogen or testosterone), with subsequent bone weakness and/or fractures. This problem necessitates the use of calcium, vitamin D, hormone replacement therapy (estrogen or testosterone), and possibly biphosphonate therapy.

Short and Long-Term Psychological Effects
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Psychological Support
Patients facing a diagnosis and treatment for cancer often have anxiety, depression, psychological distress, loss of control, and fear. These emotions are better controlled with psychological support such as counseling, group therapy or good supportive care.

All patients and survivors not only have medical problems from cancer and its therapy, but also emotional and social well-being challenges. The stress of coping with a cancer diagnosis ranges from mild to severe, often depending on the severity of the diagnosis and treatment and the prior mood of survivors. A third or more of patients report psychological distress during the early months of treatment.1,2,3 Ongoing distress levels may be similar. The prevalence of psychological distress in one study of 4496 cancer patients at John Hopkins Cancer Center was 35%.4

Mood usually improves over time for many survivors.5 Although some patients have adjusted their lives and actually feel better, others have anxiety, depression, and feelings of isolation, as well as problems interacting with friends and family. Subgroups of survivors remain vulnerable to distress or depression for a long period of time. Clinical depression affects around 18-21% survivors at various points of time.6,7 Cancer survivors who were depressed prior to their diagnosis are most at risk for shortened survival time.8

Cancer survivors are vulnerable to both acute and post-traumatic stress, a result of the life threat and loss of control experienced following diagnosis and treatment.

These responses are similar to that of the acute and post-traumatic stress syndromes, seen in soldiers on the battle front or returning from war or among those who have experienced extreme psychological or physical problems.

Clinical evaluation, counseling and educational programs offered immediately post-diagnosis and following treatment can reduce stress and lead to a better adjustment to the consequences of having cancer and its therapy. The Cancer Center at Stanford University Hospital has been a leader in offering Group Support, Individual Counseling, Massage, Medical Qigong, Restorative Yoga, Healing and Guided Imagery, Expressive Art and Imagery, Creative Writing, Healing Touch, and Exercise. Educational programs are provided, like Managing and Understanding Your Chemotherapy, Look Good and Feel Better, and Nutritional Consultations. Group therapies are provided for patients with breast cancer, brain, ovarian, colorectal, leukemia and lymphoma, patients with multiple diagnoses and for husbands of women with cancer.

Psychosocial Spiritual and Religious Support
It is of interest that an association between spirituality, survival and mortality has been noted. Cardiovascular research has shown that patients who gain comfort and strength from religion/spirituality and who participate in social and community groups, had a lower mortality rate during the six months following cardiac surgery than those who were lacking in these categories.

In a recent article in the Mayo Clinical Proceedings, Edward Creagan, M.D., wrote that "cancer survivors may be spared for reasons that are not clearly understood," and that "among the coping methods of long-term cancer survivors, the predominant strategy is spiritual. It is still recognized that the biology of a cancer is the most important determinant in the life history of a cancer course, but it is now becoming recognized that religion or spirituality may also influence the course of the cancer.

1. Bodurka-Bevers, D., Basen-Engquist, K., Carmack, C.L., et al., Depression, anxiety, and quality of life in patients with epithelial ovarian cancer, Gynecol Oncol. Sep 2000; 78 (3 Pt 1):302-308.
2. Trask, P.C., Paterson, A., Riba, M., et al., Assessment of psychological distress in prospective bone marrow transplant patients, Bone Marrow Transplant. Jun 2002; 29 (11):917-925.
3. Carlson, L.E., Angen, M., Cullum, J., et al., High levels of untreated distress and fatigue in cancer patients, Br J Cancer. Jun 14 2004; 90 (12):2297-2304.
4. Zabora, J., BrintzenhofeSzoc, K., Curbow, B., Hooker, C., Piantadosi, S., The prevalence of psychological distress by cancer site, Psychooncology, Jan-Feb 2001;10(1):19-28.
5. Ganz, P.A., Desmond, K.A., Leedham, B., Rowland, J.H., Meyerowitz, B.E., Belin, T.R., Quality of life in long-term, disease-free survivors of breast cancer: a follow-up study, J Natl Cancer Inst. Jan 2 2002;94(1):39-49.
6. Bodurka-Bevers, D., Basen-Engquist, K., Carmack, C.L., et al, Depression, anxiety, and quality of life in patients with epithelial ovarian cancer, Gynecol Oncol,. Sep 2000; 78 (3 Pt 1):302-308.
7. Fobair, P., Hoppe, R.T., Bloom, J., Cox, R., Varghese, A., Spiegel, D., Psychosocial problems among survivors of Hodgkin's disease, J Clin Oncol, May 1986; 4 (5):805-814.
8. Brown, K.W., Levy, A.R., Rosberger, Z., Edgar, L., Psychological distress and cancer survival: a follow-up 10 years after diagnosis, Psychosom Med. Jul-Aug 2003; 65 (4):636-643.

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