The number of long-term cancer survivors (5 years after diagnosis) in the U.S.continues to rise, with more than 10 million Americans now living with a history of cancer. Along with such growth has come increasing attention to the continued health problems and needs of this population. Many cancer survivors return to normal functioning after the completion of treatment and are able to live relatively symptom-free lives. However, cancer and its treatment can also result in a wide range of physical and psychological problems that do not recede with time.Some of these problems emerge during or after cancer treatment and persist in a chronic, long-term manner. Other problems may not appear until months or even years later. Regardless of when they present, long-term and late effects of cancer can have a negative effect on cancer survivors' quality of life. This article describes the physical and psychological long-term and late effects among adult survivors of pediatric and adult cancers. The focus is on the prevalence and correlates of long-term and late effects as well as the associated deficits in physical and emotional functioning. In addition, the emergence of public health initiatives and large-scale research activities that address the issues of long-term cancer survivorship are discussed. Although additional research is needed to fully understand and document the long-term and late effects of cancer, important lessons can be learned from existing knowledge. Increased awareness of these issues is a key component in the development of follow-up care plans that may allow for adequate surveillance, prevention, and the management of long-term and late effects of cancer. T he number of long-term cancer survivors (5 years after diagnosis) in the U.S. is increasing because of advances in cancer screening, early detection, treatment strategies, and management of acute treatment toxicities. Indeed, the 5-year survival rate for all cancers combined has risen to 66%, up from approximately 50% in the 1970s, 1 and it is estimated that there are now more than 10 million Americans living with a history of cancer.2 Furthermore, based partly on the overall growth and increasing average age of the U.S. population, researchers are predicting that the number of persons over the age of 65 years diagnosed with cancer each year will double by the year 2050, and will quadruple among those aged 85 years in the same time frame.3 Considered together, these factors suggest that the number of cancer survivors in this country will continue to grow and that their long-term heath problems and resulting needs will demand increasing attention.

URVIVAL RATES AFTER MYELOABlative hematopoietic cell transplantation (HCT) have improved considerably during the past 30 years. 1 The growing population of patients who have survived this treatment has intensified the need to determine the course of recovery and to identify risk factors for less favorable functional outcomes. Improved understanding of recovery will facilitate more accurate informed consent, permit better planning by patients, families, and medical teams, and enable the design of interventions to improve functional recovery.Medical complications of HCT have been well documented and include chronic graft-vs-host disease (GVHD), recurrent infection, pulmonary complications, premature menopause, cataracts, osteoporosis, avascular necrosis, infertility, recurrent malignancy, and secondary malignancy. [2][3][4][5][6][7][8][9][10] Crosssectional studies have documented functional and mental health from 1 to 10 years after transplantation but have not described the course of recovery or identified pretransplantation factors that predict recovery. [11][12][13][14][15][16][17][18][19] Other studies have been limited by lack of pretransplantation baseline assessment, 20 shorter follow-up, [21][22][23][24][25] or small sample size when follow-up extends to 3 years. 26,27 We conducted a prospective, longitudinal study to examine recovery of physical and mental health and return to work after HCT for treatment of leukemia or lymphoma. Assessments be-gan before the transplantation and continued for 5 years to identify pre-

Purpose Age has long been used as a major factor for assessing suitability for allogeneic hematopoietic cell transplantation (HCT). The HCT-comorbidity index (HCT-CI) was developed as a measure of health status to predict mortality risk after HCT. Whether age, comorbidities, or both should guide decision making for HCT is unknown. Patients and Methods Data from 3,033 consecutive recipients of HLA-matched grafts from five institutions contributed to this analysis. Patients were randomly divided into a training set to develop weights for age intervals and a validation set to assess the performance of prognostic models. Results In the training set, patients age 20 to 39 years, 40 to 49 years, 50 to 59 years, and ≥ 60 years had hazard ratios for nonrelapse mortality (NRM) of 1.21 (P = .29), 1.48 (P = .04), 1.75 (P = .004), and 1.84 (P = .005), respectively, compared with those age younger than 20 years. Consequently, age ≥ 40 years was assigned a weight of 1 to be added to the HCT-CI to constitute a composite comorbidity/age index. In the validation set, the composite comorbidity/age score had statistically significantly higher c-statistic estimates for prediction of NRM (0.664 v 0.556; P < .001) and survival (0.682 v 0.560; P < .001) compared with age, respectively. Patients with comorbidity/age scores of 0 to 2 had comparable mortality risks regardless of conditioning regimens. Patients with scores of 3 to 4 and ≥ 5 had statistically significant higher mortality risks after high-dose versus nonmyeloablative regimens. Conclusion Age is a poor prognostic factor. The proposed composite measure allows integration of both comorbidities and age into clinical decision making and comparative-effectiveness research of HCT.

Pain is a common problem in cancer survivors, especially in the first few years after treatment. In the longer term, approximately 5% to 10% of survivors have chronic severe pain that interferes with functioning. The prevalence is much higher in certain subpopulations, such as breast cancer survivors. All cancer treatment modalities have the potential to cause pain. Currently, the approach to managing pain in cancer survivors is similar to that for chronic cancer-related pain, pharmacotherapy being the principal treatment modality. Although it may be appropriate to continue strong opioids in survivors with moderate to severe pain, most pain problems in cancer survivors will not require them. Moreover, because more than 40% of cancer survivors now live longer than 10 years, there is growing concern about the long-term adverse effects of opioids and the risks of misuse, abuse, and overdose in the nonpatient population. As with chronic nonmalignant pain, multimodal interventions that incorporate nonpharmacologic therapies should be part of the treatment strategy for pain in cancer survivors, prescribed with the aim of restoring functionality, not just providing comfort. For patients with complex pain issues, multidisciplinary programs should be used, if available. New or worsening pain in a cancer survivor must be evaluated to determine whether the cause is recurrent disease or a second malignancy. This article focuses on patients with a history of cancer who are beyond the acute diagnosis and treatment phase and on common treatment-related pain etiologies. The benefits and harms of the various pharmacologic and nonpharmacologic options for pain management in this setting are reviewed.

PURPOSE Hematopoietic cell transplantation can cure hematologic malignancies and other diseases, but this treatment can also cause late complications. Previous studies have evaluated the cumulative effects of late complications on survival, but longer-term effects on life expectancy after hematopoietic cell transplantation have not been assessed. PATIENTS AND METHODS We used standard methods to evaluate mortality, projected life expectancy, and causes of death in a cohort of 2,574 patients who survived without recurrence of the original disease for at least 5 years after allogeneic or autologous hematopoietic cell transplantation from 1970 through 2002. Sex- and age-specific comparisons were made with US population data. Results Estimated survival of the cohort at 20 years after transplantation was 80.4% (95% CI, 78.1% to 82.6%). During 22,923 person-years of follow-up, 357 deaths occurred. Mortality rates remained four- to nine-fold higher than the expected population rate for at least 30 years after transplantation, yielding an estimated 30% lower life expectancy compared with that in the general population, regardless of current age. In rank order, the leading causes of excess deaths were second malignancies and recurrent disease, followed by infections, chronic graft-versus-host disease, respiratory diseases, and cardiovascular diseases. CONCLUSION Patients who have survived for at least 5 years after hematopoietic cell transplantation without recurrence of the original disease have a high probability of surviving for an additional 15 years, but life expectancy is not fully restored. Further effort is needed to reduce the burden of disease and treatment-related complications in this population.

Although indistinguishable in many respects, survivors had more medical needs than controls. Health problems were not focused on specific diseases or limited to survivors with readily identifiable risk factors. Musculoskeletal problems require both screening and research into etiologies and effective treatments. Osteoporosis and hypothyroidism may be underdiagnosed. Survivors require screening for sexual problems, urinary frequency, mood and need for antidepressants or benzodiazepines.

The Ancillary Therapy and Supportive Care Working Group had 3 goals: (1) to establish guidelines for ancillary therapy and supportive care in chronic graft-versus-host disease (GVHD), including treatment for symptoms and recommendations for patient education, preventive measures, and appropriate follow-up; (2) to provide guidelines for the prevention and management of infections and other common complications of treatment for chronic GVHD; and (3) to highlight the areas with the greatest need for clinical research. The definition of "ancillary therapy and supportive care" embraces the most frequent immunosuppressive or anti-inflammatory interventions used with topical intent and any other interventions directed at organ-specific control of symptoms or complications resulting from GVHD and its therapy. Also included in the definition are educational, preventive, and psychosocial interventions with this same objective. Recommendations are organized according to the strength and quality of evidence supporting them and cover the most commonly involved organs, including the skin, mouth, female genital tract, eyes, gastrointestinal tract, and lungs. Recommendations are provided for prevention of infections, osteoporosis, and steroid myopathy and management of neurocognitive and psychosocial adverse effects related to chronic GVHD. Optimal care of patients with chronic GVHD often requires a multidisciplinary approach.

The 2006 National Institutes of Health (NIH) Consensus paper presented recommendations by the Ancillary Therapy and Supportive Care Working Group to support clinical research trials in chronic graft-versus-host disease (GVHD). Topics covered in that inaugural effort included the prevention and management of infections and common complications of chronic GVHD, as well as recommendations for patient education and appropriate follow-up. Given the new literature that has emerged during the past 8 years, we made further organ-specific refinements to these guidelines. Minimum frequencies are suggested for monitoring key parameters relevant to chronic GVHD during systemic immunosuppressive therapy and, thereafter, referral to existing late effects consensus guidelines is advised. Using the framework of the prior consensus, the 2014 NIH recommendations are organized by organ or other relevant systems and graded according to the strength and quality of supporting evidence.