Long Term Toxicity of Cancer Treatment in Older Patients

Synopsis

With earlier cancer diagnosis among older cancer patients, the possibility of curing cancer increases. However, cancer treatment may have long lasting impact on older cancer survivors. It is vital to screen, diagnose and properly manage the long term toxicities of cancer treatment, in order to maintain quality of life of older cancer survivors

Introduction

The number of cancer survivors is increasing in the United States. In 2014, there were 14.5 million cancer survivors. By 2024, this number is expected to increase to 19 million with the significant portion of them being older than age 65 ¹. As more patients are diagnosed with earlier stages of cancer, the likelihood of cancer survivors living beyond 5 years after the initial cancer diagnosis has increased. ² The role of primary care providers in the immediate and long-term follow up of cancer patients are still being defined, as there are significant differences between primary care providers and oncologists’ preferences toward follow up care of the cancer survivors. While 38% of primary care providers prefer shared care of the cancer survivors with the oncologists, only 16% of oncologists were in agreement with this model of care. More than half of primary care providers thought they have necessary skills to take care of the cancer survivors, while this was agreed to by only 23% of the oncologists ³. The primary care providers who were more confident in their skills to provide follow-up care for cancer patients, were more involved in the cancer patients’ care ⁴.

Interaction between aging, cancer, cancer treatment, and their impact on frailty

Frailty, broadly defined, is a state of decreased (or total lack of) reserve and resistance to physical and emotional stressors, due to continuous decline in various organ functions ⁵. As patients age, they tend to become more frail, although aging and frailty do not correlate with each other all the time ⁶. Cancer patients are more likely to be frail compared to non-cancer patients ^7,8. Moreover, cancer treatment, itself, can lead to frailty ⁹. (Figure 1)

Figure 1.

Impact of aging, cancer, and cancer treatment on patients’ fitness and frailty.

Measuring frailty and geriatric deficits

Comprehensive Geriatric Assessment (CGA) (Table-1) performed by healthcare providers has been a useful tool to assess and manage frailty and geriatric deficits among older cancer patients and survivors ^10,11. In the cancer setting, the data on usefulness of CGA in predicting short term toxicities of chemotherapy ^12,13, complications and outcome after cancer surgery ^14,15, and cancer treatment decision-making ^16,17 is emerging.

Table 1.

Components of Comprehensive Geriatric Assessment

Components of Comprehensive Geriatric Assessment
Activities of Daily Living (ADL)
Instrumental Activities of Daily Living (iADL)
Cognition
Social Support
Polypharmacy
Nutrition
Comorbid conditions
Emotional distress, Depression

Therapy for elderly cancer patients

For many years, cancers were treated by surgery, chemotherapy, radiation, or hormonal treatments. Over the last 10–15 years, new class of cancer treatment has emerged which is known as targeted therapy ¹⁸. Considering the differences with the standard and well-known chemotherapy drugs regarding their route of administration, duration of treatment, and toxicity profile, this class of drug is discussed separately. Table 2 discusses basic facts on medical cancer treatment. In the next sections, we will discuss long-term toxicities of cancer treatment. Table 3 provides information for screening, diagnosis and management of each of long-term toxicities.

Table 2.

Basics of medical cancer treatment

1- Context		Timing	Goal
	A- Neoadjuvant	Administered before definitive surgery.	To shrink the tumor so that surgery becomes feasible or easier
	B- Adjuvant	After definitive surgery	To treat microscopic disease, and to delay recurrence.
	C- Palliative	Advanced cancer	Relieving symptoms (e.g. pain, shortness of breath, and to slow the progression of the disease.
2- Route
	A- Intravenous	Majority of cancer treatment
	B- Oral agents	Mainly targeted therapies (e.g. Erlotinib, Lapatinib, Pazopanib)
	C- Subcutaneous	Very few (e.g. Bortezomib for Multiple Myeloma)
	D- Intramuscular	Very few (e.g. Fulvestrant for breast cancer, Leuprolide for prostate cancer)
3- Number of agents
	A- Multiple	Majority of chemotherapy regimens. At times, it is combined with targeted agents as well. In general, combined chemotherapy is more toxic than single agent chemotherapy. Used in neoadjuvant, adjuvant, and palliative setting
	B- Single	Mainly used in the palliative setting. In frail patients, it can be used in the adjuvant setting.
4- Dose
	A- Standard	The concern over using standard dose in the elderly patients is due to limited number of older patients enrolled in the clinical trials. Many of those who are enrolled are not a true representation of community dwelling older patients with cancer.
	B- Dose reduced

Table 3.

Long-term toxicity of cancer treatment, approach, and management.

Toxicity	Diagnosis / screening	Management
Cognitive impairment	Mini-Cog 114, Mini Mental Status Exam 115, Montreal Cognitive Assessment 116	Rule out reversible causes of cognitive deficit (depression, hypothyroidism, vitamin B12 and folic acid deficiency) Referral to cognitive rehabilitation 117, when possible
Cardiotoxicity	Electrocardiogram, Echocardiogram, stress test	Control other risk factors for cardiac condition (e.g. hypertension management, smoking cessation, lipid control, etc.)
Depression & Anxiety	Distress thermometer 118 Geriatric Depression Scale (GDS) 119, Patient Health Questionnaire (PHQ) 120	Cognitive behavioral and stress management 121, when possible Psychoeducational interventions to cope with stress 122 Selective serotonin reuptake inhibitor 123 Encouraging patients to be more physically active 124.
Ototoxicity	Hearing Handicap Inventory for the Elderly- Screening Version 125,126	Rule out other causes of hearing impairment (cerumen impaction, chronic otitis media) Referral to audiologists and otolaryngologists to assist with the diagnosis and proper hearing aides 127.
Imbalance and lack of coordination	Mostly clinical. In rare circumstances, may consider NCV/EMG, skin and nerve biopsy to confirm the diagnosis 44.	Control other causes of neuropathy (e.g. diabetes, vitamin B12 deficiency) Treatment with Duloxetine 42 or venlafaxine 128 Referral to physical and occupational therapy 129,130.
Osteoporosis	Bone densitometry 131 WHO Fracture Risk Assessment Tool (FRAX)	Life style modifications: weight bearing exercises 132, Tai Chi 133. Home safety inspection134 Vitamin D and calcium supplement 135 Starting Bisphosphonates in patients with proven osteoporosis or fracture136
Metabolic Syndrome	Assessment of weight, blood pressure, and waist circumference, measurement of glucose and lipid panel	Recommendation for smoking cessation 137, excessive alcohol abstinence, healthy diet 138, and more physical activity 139
Second malignancies	Assessment of symptoms not controlled with the conservative management Routine blood cell count Adherence to cancer screening guidelines	Referral to medical oncologist.
Sexual and vaginal dysfunction	History taking (e.g. Erectile dysfunction, Dyspareunia) and pelvic examination (e.g. discomfort on examination, pelvic floor weakness)	Vulvovaginal atrophy: vaginal lubricants and moisturizers, topical or systemic estrogen therapy (for non-hormone dependent cancers) Pelvic floor weakness: pelvic floor exercises, chronic pad use Vaginal pain or stenosis: dilators

Data from Refs 42, 44, 114–139.

Chronic Toxicity from Cancer Therapy

1. Cardiotoxicity

Cardiotoxicity can present itself in various ways (Table 4). In general, patients with preexisting cardiac conditions are at higher risk for developing cardiotoxicity in the short -and long-term ¹⁹. Among breast cancer patients, the incidence of cardiotoxicity is 3 to 35% ²⁰, and at times it competes with breast cancer for leading cause of death. ²¹ Anthracyclines (e.g. doxorubicin), frequently used chemotherapy agents in breast cancer patients, can cause cardiotoxicity even at low doses in patients with preexisting cardiac conditions ²². These patients are 5.4 and 6.25 times more likely to develop clinical and subclinical cardiotoxicity compared to those who did not receive anthracycline, respectively ²³. More importantly, the risk of cardiac death was 4.94 times more compared to those who did not receive anthracycline. Older patients are at higher risk for developing cardiotoxicity, as for each 10-year increase in age, the risk of developing congestive heart disease doubled. ²⁴

Table 4.

Cardiotoxicity of cancer treatment.

Cardiotoxicity	Note	Drugs
1- Heart Failure (left ventricular dysfunction)	Most common	Anthracyclines Alkylating agents (e.g. cyclophosphamide) Inhibitors of microtubule polymerization (e.g. paclitaxel) Monoclonal antibodies (e.g. trastuzumab)
2- Newly induced or worsening hypertension	Class effect of VEGF inhibitors	Bevacizumab
3- Cardiac ischemia		Antimetabolites (e.g. 5-FU) Inhibitors of microtubule polymerization (e.g. paclitaxel) Targeted agents (e.g. bevacizumab)
4- Arrhythmia	QT prolongation, Torsade de pointes	Arsenic Trioxide Most of anti-emetics drugs

VEGF: Vascular Endothelial Growth Factor

Prostate cancer patients on ADT may also have more cardiotoxicity, compared to those not on ADT ^25,26. For every year increase in age, the risk of cardiac comorbidity increases by 3% ²⁷. The 5-year cumulative risk of dying from cardiac causes in patients on ADT after prostatectomy reaches 5.5% compared to 2% of patients who only underwent prostatectomy ²⁸. Patients receiving 5-fluouracil (5-FU) are also at higher risk for cardiotoxicity. 5-FU can cause cardiotoxicity in 1.2% to 18% of patients. The toxicity is usually short term and occurs while patient is receiving 5-FU ²⁹. Capecitabine, an oral derivative of 5-FU, can also cause ischemia in up to 9% of patients ³⁰. These toxicities are usually short term.

2. Emotional effects (depression, anxiety)

Cancer patients experience emotional disturbances even years after completion of the treatment. About 57% of patients with gynecologic cancer reported that they need help in dealing with cancer-related emotions, however only 35% had received such help, and 73% believed that physicians should ask whether patients with cancer want help in dealing with emotions ³¹. At least 11.6% and 17.9% of long term cancer survivors are suffering from depression, and significant level of anxiety ³². In extreme cases, patients may have suicidal ideation if distress and depression remain undiagnosed, and untreated ³³.

3. Ototoxicity

Platinum agents (e.g. cisplatin) can cause ototoxicity ³⁴. Ototoxicity can present itself as permanent bilateral hearing loss and/or tinnitus. Among platinum agents, cisplatin is the most common chemotherapeutic agent to cause ototoxicity, resulting in bilateral hearing loss and/or permanent tinnitus in 19 to 79% of the patients ³⁵. Older patients with hearing difficulty are at higher risk for falls ³⁶, accelerated cognitive decline ³⁷, and poor quality of life ³⁸.

4. Balance and coordination

Lack of balance and falls may occur in cancer patients and can lead to injuries such as bone fracture ³⁹. Maintaining proper balance is a result of complex interaction between cognition ⁴⁰, orientation to space, biomechanical changes, and sensors ^39,41. Chemotherapy induced peripheral neurotoxicity (CIPN) may happen in 20 to 40% of cancer patients receiving neurotoxic chemotherapy agents ⁴², and can increase risk of falls and associated fractures in cancer survivors ⁴³. Taxanes and platinum agents are the most common drugs that can cause CIPN ^44–46. Patients with preexisting neurological deficits such as diabetic neuropathy are at higher risk for developing CIPN ⁴⁷. Most common presenting symptoms are numbness and tingling especially in the lower limbswhich at times could be painful ^48,49. Vinca alkaloids (vincristine, vinblastine, vinorelbine) and bortezomib can also cause significant chronic neurotoxicity ⁵⁰.

5. Effect on muscle and bone health

Cancer survivors are at higher risk for osteoporosis compared to the general population ⁵¹, and as a result, they are at higher risk for fractures ⁵². Certain breast cancer treatments increase the risk of osteoporosis. Up to 70% of patients may experience menopause during adjuvant chemotherapy for breast cancer. The earlier the induced menopause occurs, the higher the risk of osteoporosis ⁵³. Many older breast cancer patients receive adjuvant hormonal therapy. While tamoxifen is associated with a decreased risk of osteoporosis if used in postmenopausal women, it may lead to an increase in the incidence of osteoporosis in premenopausal women ⁵⁴. Compared to tamoxifen, aromatase inhibitors (AIs) are associated with higher risk of low bone density and fractures ⁵⁵. Surgical or medical ovarian ablation also leads to a decrease in estrogen production resulting in bone loss ⁵⁶. Prostate cancer survivors are also at high risk for developing osteoporosis. In one study, five years after diagnosis of prostate cancer and receiving ADT, 19.4% of the patients suffered a fracture ⁵⁷. In another study, prostate cancer survivors were at least 2.49 times more likely to have osteoporosis compared to those without prostate cancer ⁵⁸. Despite higher risk for osteoporosis and fracture, one study showed that 77% of survivors with osteoporosis were undiagnosed by their primary care providers ⁵⁹. This finding has been confirmed by other studies ^58,60,61. The American Society of Clinical Oncology (ASCO) ⁶² and National Comprehensive Cancer Network (NCCN) ⁶³ have proposed guidelines for diagnosis and management of the osteoporosis in cancer patients.

6. Metabolic Syndrome

Metabolic syndrome (MS) is a constellation of states that increases the risk of cardiovascular events, diabetes, fatty liver, and sleep disturbances ⁶⁴. The majority of the studies on incidence of MS in long term cancer survivors have focused on testicular and early adulthood diagnosis of leukemia / lymphoma ^65,66. Two known causes of the MS are testosterone ⁶⁷ and estrogen deficiency ⁶⁸. In one study, 50% of men with prostate cancer receiving long term ADT had MS ⁶⁹. Another study on men with recurrent or locally advanced prostate cancer receiving leuprolide for 12 months showed that the mean weight, body mass index, waist circumference, and fat mass increased , while the percentage of lean body mass decreased compared to the baseline ⁷⁰. Breast cancer survivors are also at higher risk for development of MS. A study of 53 breast cancer survivors showed that compared to surgery alone, patients undergoing chemotherapy are at higher risk for weight gain, increase in body fat percentage and fat mass, and decrease in lean body mass ⁷¹. Breast cancer survivors with MS are at higher risk for cancer recurrence than those without MS ⁷².

7. Secondary malignancies:⁷³

Cancer survivors are at high risk to develop second cancers ⁷⁴. This increased risk could be due to genetic predisposition, consequence of previous cancer treatment, undergoing surveillance following first cancer treatment completion, or environmental factors ^75,76. In particular patients who receive chemotherapy are at 4.7 fold higher risk for developing treatment-related acute myeloid leukemia (AML) compared to the general population. Nearly half of 801 treatment-related AML from 1975 to 2008 occurred in breast or non-Hodgkin Lymphoma (NHL) survivors ⁷⁷. Patients who have received topoisomerase II inhibitors (e.g. doxorubicin, etoposide, irinotecan) usually develop leukemia within 5 years, and those who receive alkylating agents (e.g. cyclophosphamide) develop leukemia after 5 years ⁷⁸. The incidence of leukemia also correlates with the dose of chemotherapy patients receive ^79,80. Hodgkin lymphoma survivors are particularly at high risk for developing leukemia ⁸¹ which is particularly related to dose of alkylating agents. Although with recent treatments ⁸², the incidence of leukemia has been shown to have decreased, it still is worth considering when taking care of the cancer survivors. In similar fashion, patients with non-Hodgkin lymphoma are at higher risk for developing leukemia within 10 years of treatment completion ⁸³.

8. Sexual and Vaginal Dysfunction

Cancer and its associated treatment can have a devastating effect on vaginal health and sexuality. Disease type, stage of disease, and type of treatment can contribute or compound atrophy of the vagina and vulvar tissues, resulting in painful gynecological exams, sexual difficulties, and other long-term issues ^84–87 Estrogen deprivation effects include vulvovaginal atrophy (VVA), with the loss of genital tissue elasticity and lubrication, and symptoms of dryness, irritation, itching, discharge, and dyspareunia. Estrogen-deprivation-associated VVA can lead to loss of sexual desire and arousal, and orgasm difficulties stemming from vaginal dryness, pain, and stenosis ⁸⁸ Older cancer patients may mistakenly believe that sexual/vaginal changes are an inevitable result of aging rather than recognizing that cancer treatment may be a contributing factor ⁸⁹ For example, many women treated with extended endocrine therapy, specifically aromatase inhibitors (AIs), develop vaginal dryness, gross architectural vulvar changes, etc.. Radiation therapy to the pelvis can cause agglutination, ulceration, stenosis, scarring , and a reduction in vaginal depth, elasticity and sexual function Long-term bowel issues and fear of urinary and fecal incontinence post-treatment are significant concerns that can also interfere with sexual activity. Furthermore, radical vulvar excisions are significantly associated with lower sexual function and quality of life, particularly in older women. Patients have indicated a need for basic advice on the prevention and treatment of vaginal and sexual toxicities and welcome discussions on these topics with their doctors These issues do not spontaneously resolve over time without appropriate intervention Early identification and treatment strategies are essential in addressing these long-term challenges; physician-patient communication is imperative, and may be enhanced with the use of brief surveys and checklists⁹⁰

9. Fatigue

One of the most common long term side effects of cancer therapy is fatigue. The symptom of fatigue that the cancer patient experiences is different from the symptoms that health people experience. The feelings of fatigue that healthy people feel is often alleviated by sleep and rest. Patients who have undergone cancer treatment get fatigued after less activity than those who had had cancer. Fatigue can definitely affect quality of life. The cause of this symptoms is multifactorial and can include the long term affects of therapy (chemotherapy, radiation, biologic therapy, surgery, etc.), anemia, nutrition, anxiety and depression, sleep disorders and drugs. Polypharmacy which is common in the elderly can contribute. Specific drugs such as anxiolytics, sleeping medicine, narcotics, drugs which treat neuropathy (gabapentin, pregabalin) contribute to this syndrome. Pharmacologic interventions have been unsuccessful unless a specific diagnosis (ie. depression) can be made ⁹¹.

10. Cognitive Impairment

Many patients undergoing chemotherapy complain of cognitive changes (chemotherapy-related cognitive impairment [CRCI]) ⁹². These complaints are usually broad and range from distraction, lack of focus, to inability to perform daily cognitive routines (e.g. paying bills) ⁹³. Although at times subjective complaints do not correlate with the objective assessments ⁹⁴, it is vital to appreciate such complaints. The majority of studies on CRCI have been conducted in breast cancer survivors. In this setting, cognitive deficit usually involves certain domains of cognition (e.g. verbal ability or visuospatial) ⁹⁵ which could be long lasting ⁹⁶. It can develop after completion of the treatment ⁹⁷, however, in some cases, cognition may improve following completion of the treatment ⁹⁸. Hormone receptor positive breast cancer patients usually take anti-estrogen treatments (e.g. tamoxifen, exemestane) which may impact their cognition. Patients on the 5-year tamoxifen regimen reported memory complaints more than those who were not taking tamoxifen ⁹⁹. As with chemotherapy, cognitive deficit occurred in specific domains of cognition (verbal memory, verbal functioning, verbal fluency and information processing speed) ^100,101. The other common cancer is prostate cancer. Patients may require androgen deprivation therapy (ADT) aiming at reducing the testosterone level. About half of prostate cancer patients on ADT could have cognitive decline in at least one domain of cognition ^102,103. Like breast cancer treatment, prolonged use of ADT leads to decline in specific domains of cognition as noted previously ¹⁰⁴. Patients with other types of cancer (e.g. colorectal) experience the same phenomena ¹⁰⁵.

Effect of other modalities

1. Targeted Therapies

In the past 10–15 years, the emergence of a new class of cancer treatment known as targeted agents has changed the spectrum of cancer treatment. In some instances, patients with metastatic disease can receive targeted agents for months or even years. In brief, targeted therapies are either monoclonal antibodies to certain proliferation or anti-apoptotic proteins, or are inhibitors of pathways that signal cell proliferation ¹⁸. These therapies are not often associated with long-term toxicities. Many of the adverse events are short lived or reversible (Table 5). The most common targets for these agents are Epidermal Growth Factor Receptor (EGFR), Vascular Endothelial Growth Factor (VEGF), Human Epidermal Receptor-2 (HER-2), mammalian target of rapamycin (m-TOR) and BRAF kinase. Agents that target EGFR can cause skin rash, diarrhea, and electrolyte abnormalities (e.g. hypomagnesemia). The toxicity of VEGF targeted agents include hypertension, fatigue, wound healing, and thrombosis. Due to vascular toxicity they are associated with increased risk in older patients ¹⁰⁶. m-TOR inhibitors, especially temsirolimus can cause hyperlipidemia and hyperglycemia. Those who take BRAF inhibitors can develop skin cancer. Trastuzumab is associated with cardiomyopathy.

Table 5.

Toxicities of targeted agents.

Cancer	Name of agent	Target	Common side effects
Non-small cell Lung Cancer	Erlotinib Gefitinib Crizotinib	EGFR EGFR ALK-4	Rash, fatigue, appetite loss Rash, diarrhea Edema, fatigue, diarrhea, visual disturbances
Renal cell carcinoma	Sunitinib pazopanib Temsirolimus Axitinib	Mutikinase Multikinase m-TOR VEGF	Hand and foot syndrome, hypertension, fatigueRash, edema, hyperlipidemia, hyperglycemia Hypertension, fatigue, diarrhea Hypertension, rash, diarrhea, fatigue
Colorectal cancer	Cetuximab Panitumumab Regorafenib Aflibercept	EGFR EGFR Kinase, VEGF VEGF	Rash, diarrhea Rash, diarrhea Hypertension, Fatigue, hand and foot syndrome, proteinuria Hypertension, fatigue, diarrhea.
Breast Cancer	Trastuzumab Pertuzumab Trastuzumab emtansine (T-DM1) Lapatinib	HER2 HER 2 HER 2 Kinase	Heart failure Diarrhea, skin rash, heart failure Fatigue, skin rash, arthralgia, heart failure Skin rash, hand and foot syndrome, diarrhea
Renal cell carcinoma, hepatocellular carcinoma	Sorafenib	Multikinase	Hypertension, diarrhea, fatigue, hand and foot syndrome
Colorectal cancer, Ovarian cancer	Bevacizumab	VEGF	Hypertension, thrombosis, proteinuria , delayed wound healing
Renal cell carcinoma, Breast cancer	Everolimus	m-TOR	Stomatitis, diarrhea,
Melanoma	Vemurafenib Dabrafenib Ipilimumab	BRAF kinase BRAF kinase CTLA-4	Fatigue, arthralgia, skin cancer Fatigue, fever, arthralgia Immune-mediated reactions (diarrhea, fever, fatigue, etc…)
Chronic Myeloid Leukemia, Gastrointestinal Stromal Tumors (GIST)	Imatinib	Kinase	Edema, diarrhea, rash.

EGFR: Epidermal Growth Factor Receptor, m-TOR: Mammalian target of rapamycin inhibitor, HER: Human Epidermal Receptor, VEGF: Vascular Endothelial Growth Factor , CTLA4: Cytotoxic T-Lymphocyte-associated protein 4.

2. Long term toxicities of radiation

Radiation therapy has a substantial role in treating many prevalent and frequently curable malignancies, notably breast and prostate cancer. Radiotherapy can induce chronic, nonlethal changes in non-proliferating normal tissues, with fibrosis being the prototypical example. The potential late toxicities in a given patient depend upon the anatomic region, volume of tissue that was irradiated, radiation dose and use of concurrent chemotherapy. Modern tools such as intensity-modulated radiation therapy (IMRT), image-guided radiation therapy, and proton therapy reduce the incidence and severity of late toxicity.

Central Nervous System

Brain radiation is most commonly employed for patients with brain metastases or for gliomas. However, brain radiation is also utilized for less lethal tumors such as meningioma. Studies indicate that short-term memory is the faculty most likely to be chronically impaired when radiating the brain ¹⁰⁷. Stereotactic radiosurgery, which can treat meningiomas, isolated brain metastases, or benign conditions such as arteriovenous malformations, also carries a risk of necrosis in the brain tissue adjacent to the target. This can cause seizures or focal neurologic deficits, months or years after treatment ¹⁰⁸.

Neck and upper aerodigestive tract

Radiation therapy is often employed as curative or post-surgical treatment of primary head and neck tumors. Though highly effective and often allowing for organ preservation, radiation therapy to this region is associated with perhaps the most frequently apparent late radiation toxicity. Permanent xerostomia due to incidental irradiation of the parotid glands is very common and significantly impacts patient quality of life. Fibrosis of the skin and connective tissue can lead to trismus and restricted range of motion in the neck. Hypothyroidism is commonly induced by head-and-neck radiotherapy, and incidence of carotid artery stenosis after radiation has been reported as high as 50% ¹⁰⁹. Brachial plexus injury is also possible.

Thorax

Breast or chest-wall radiation for breast cancer is among the most common indications for radiation therapy and long-term survival is likely. The most common late effects include poor cosmesis (e.g. skin hyperpigmentation), fibrosis limiting range of motion in the arm, and lymphedema. Radiation pneumonitis, which is a delayed inflammatory response to lung irradiation, is a subacute toxicity typically occurring within a few months to one year after radiotherapy. It can recur and increase the risk of radiation fibrosis, which is a chronic scarring and inactivation of lung tissue. Radiation pneumonitis is typically treated successfully with corticosteroids, but there is no established therapy for radiation-induced lung fibrosis ¹¹⁰.Cardiac irradiation increases the risk of heart disease, as has been apparent from the experience with long-term survivors of Hodgkin lymphoma, and also from patients with left-sided breast cancer ^111,112.

Gastrointestinal

The largest population of gastrointestinal patients with potential late radiation toxicity is rectal cancer patients, owing to the routine use of preoperative radiation in this prevalent and frequently cured disease. Pelvic radiation therapy can diminish bowel function, leading to chronic diarrhea, rectal bleeding, or incontinence ¹¹³. Radiotherapy to the abdomen or pelvis also increases the risk of small bowel obstruction. Radiation for pancreatic and esophagogastric cancers increases the risk of serious mucosal injury to the stomach, duodenum, or bowel.

Conclusion

The aging of the population and the success of cancer therapy has resulted in a large number of older cancer survivors. The chronic toxicity of therapy combined with the comorbidities seen in this population make long term management challenging. To provide optimum care, survivorship guidelines are being formulated. This will provide the oncologist, primary care physician and geriatrician an organized framework to take care of these patients. In 2005, the Institute of medicine published a report entitled “From cancer patient to cancer survivor: Lost in transition". This report describes recommendations for ongoing guidelines for cancer survivors, the cancer team, primary care physicians, and other healthcare providers. The report recommends that at the completion of cancer treatment, clinicians provide a Survivorship Care Plan that includes the summary of treatment delivered and a detailed plan of ongoing care, as well as surveillance guidelines, potential late effects, and potential behavioral modifications that patients can make such as weight management, alcohol and regular exercise (https://www.iom.edu/Reports/2005/From-Cancer-Patient-to-Cancer-Survivor-Lost-in-Transition.aspx; accessed June 28, 2015).

Key Points.

• The number of older cancer survivors is expected to rise in the next few decades due to aging population, earlier cancer stage diagnosis, and proper cancer treatment.

• Although effective on cancer treatment, both chemotherapy and radiation therapy may have long lasting negative impact on older cancer survivors’ quality of life.

• Long term toxicities of breast and prostate cancer treatment on cognition, cardiac function, emotional wellbeing, muscle and bone health, balance and coordination, and sexual health are well known.

• In order to maintain older cancer survivors’ quality of life, it is critical that primary care providers screen, diagnose, and properly manage long term toxicities of cancer treatment.