Long-term Follow-up Guidelines Research Articles

Reply to P.J. Leary et al

We thank Leary et al for their thoughtful comments regarding our article. Because a growing number of survivors of childhood cancer who have received treatment that may damage the heart and/or lungs are now aging through early and middle adulthood, it is increasingly important to thoroughly describe the onset and trajectory of cardiopulmonary toxicity, the second most common cause of treatment-related mortality in aging survivors. Our data suggest that some survivors, on the continuum of progression to cardiopulmonary failure, may develop pulmonary hypertension. We hope that by documenting this next stage of cardiopulmonary failure, we have highlighted the need for additional research that identifies the etiology of pulmonary hypertension in this population and establishes directions for therapeutic intervention. We strongly agree with Leary et al that the results of our study should not be misinterpreted as an analysis of the frequency of pulmonary arterial hypertension (WHO group I pulmonary hypertension) among adult survivors of childhood cancer. As Leary et al state, the current analysis suggests that left-sided heart failure may be the etiology of the increased tricuspid regurgitant jet velocity, consistent with WHO Group II pulmonary hypertension. However, it is notable that the analysis also suggests that pulmonary hypertension was associated specifically with chest-directed radiotherapy, but not anthracycline exposure, a common cause of left-sided heart failure among adult survivors of childhood cancer. There remains the possibility that direct radiation injury to the pulmonary arterial vasculature (WHO group I, pulmonary arterial hypertension) may contribute to the etiology of the current findings. The potential for direct vascular injury from radiotherapy is well established. Additionally, direct radiation to the lung parenchyma (WHO group III) may also contribute. Our survivor population was evaluated using the Children’s Oncology Group Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers. Thus, pulmonary function testing was not performed on all of the participants in our study, which reduces the statistical power of our analysis to determine the contribution of direct pulmonary injury. Future research should incorporate a complete assessment of pulmonary function among survivors who are at risk of treatment-associated cardiac dysfunction to further define the potential contribution of pulmonary toxicity in the observed elevations in tricuspid regurgitant jet velocity. We also agree with Leary et al that research collaboration among oncologists, cardiologists, and pulmonary vascular experts will be necessary to unravel the potentially complex etiology of elevated tricuspid regurgitant jet velocity among adult survivors of childhood cancer. Right heart catheterization augmented by exercise testing will be the next step in validating these findings, determining etiology, and most importantly, directing appropriate medical therapy. More comprehensive evaluation and continued follow-up of the St Jude Lifetime Cohort will allow us to clarify these issues and determine the impact of elevated tricuspid regurgitant velocity on subsequent morbidity and mortality.

Cardiotoxicity in childhood cancer survivors: A problem with long-term consequences in need of early detection and prevention

I n this issue of Pediatric Blood & Cancer, Orgel et al. [1] report the prevalence of early post-treatment cardiac dysfunction in a multi-center, retrospective cohort of childhood acute myeloid leukemia (AML) survivors. After a median follow-up of 13 months from the end of treatment, patients demonstrated an 8.7% decline in left ventricular shortening fraction (LVSF) from baseline to the most recent post-treatment echocardiogram. Further, declines in LVSF greater than 10% were found in more than half of the cohort [1]. These declines were significantly associated with cumulative anthracycline dose, body-mass index percentile, and ethnicity. The authors conclude that children treated with an anthracycline-intensive regimen are at risk of late-onset cardiomyopathy, should be monitored with echocardiograms annually, and should be considered for cardioprotective strategies [1]. Cumulative anthracycline dose, age at diagnosis, gender, and length of follow-up, are all associated with late anthracyclineassociated cardiac dysfunction [2]. Although the anthracyclines used in this study were daunorubicin or mitoxantrone (mg/m), the authors used doxorubicin-equivalent doses to calculate anthracycline exposure, resulting in a mean cumulative anthracycline dose of 339 14mg/m. The findings of this study support that anthracycline-induced cardiotoxicity is dose-dependent, such that every 100mg/m increase in cumulative anthracycline dose was accompanied by a percent decrease of 7.4% (95% CI 11.1 to 3.7) in LVSF. Further, both this study and others [3] report declines in cardiac function even in children who received lower cumulative doses, suggesting that there is no risk-free dose of anthracycline. Shortening fraction is a measure of overall left ventricular (LV) systolic performance, which is influenced by heart rate, preload (initial stretching of the cardiomyocytes prior to contraction), afterload (the ventricular wall stress during ejection), and myocardial contractility. A decrease in LVSF at the end of anthracycline therapy is not uncommon in childhood cancer survivors, and is associated with decreased LVSF 11 years after diagnosis [3]. However, a more thorough evaluation of cardiac structure and function might include additional echocardiographic measures, such as LV mass and end-diastolic posterior wall thickness, which are also affected by anthracycline therapy. For example, LV mass and wall thickness are significantly reduced at 3, 6, and 8 years after diagnosis [4]. Altogether, these findings suggest there is a progressive and persistent deterioration of heart structure and function with time. While researchers and clinicians agree that there is a need for established guidelines to monitor cardiac function in these children, there is still a lack of evidence-based research determining the most effective mode and frequency of serial monitoring. Echocardiography, a minimally invasive method of measuring cardiac structure and function, is a useful and common modality used to monitor these children, but has limited sensitivity and specificity. The Children’s Oncology Group’s Long-Term Follow-Up Guidelines [5], referred to by Orgel et al., are based on recommendations from their core committee and is intended to standardize follow-up care in survivors of childhood cancers. They recommend echocardiograms or MUGA scans in varying frequencies depending on a child’s age at treatment, radiation exposure to the heart, and anthracycline dose. Further evidence-based research is required to validate these guidelines. Although they do not include gender, all of the other previously mentioned variables are generally the most common risk factors of cardiotoxicity. Given the varying frequency and severity of cardiotoxicity even among children receiving the same dose, researchers suspect there are still unknown risk factors that may influence cardiotoxicity, such as genetics, and as Orgel et al. [1] showed, body-mass index and ethnicity. Although echocardiographic measures help assess heart structure and function during therapy, it lacks the sensitivity and specificity to detect early cardiac injury and the ability to distinguish between short-term depressions in LV function and myocardial injury with late cardiac implications. Biochemical markers of cardiac injury and cardiomyopathy, such as cardiac troponin T (cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP), respectively, may also be useful in monitoring cardiotoxicity. Although not yet validated for clinical utility, elevations of these biomarkers during treatment are associated with abnormal echocardiographic findings 4 years after diagnosis [6]. As noted by Orgel et al., further efforts are needed to determine the validity and cost-effectiveness of using cardiac biomarkers and other screening models to predict cardiotoxicity [7]. The challenge lies in the ability to prospectively follow these children long enough to where sufficient vital status end points can be reached to reliably quantify the relationship between markers of cardiac injury and outcome.

Screening tool for late‐effect pediatric neuro‐oncological clinics: A treatment‐oriented questionnaire

Many survivors of pediatric brain tumors (SPBTs) suffer from long-term late effects (LEs). Our aim was to create a practical screening tool for detecting LEs in this population. Such a screening tool will improve our ability to identify those patients who may benefit from treatment in LE clinics while focusing on individual relevant issues. We developed the Treatment-Oriented Screening Questionnaire (TOSQ); a self-reported, risk-based questionnaire that addresses all LEs SPBTs can potentially suffer. As a basis for the TOSQ design we used the Long-Term Follow-Up Guidelines published by the Children's Oncology Group. Output includes individual recommendations for further treatment. We prospectively assessed whether the TOSQ can accurately detect treatment targets in SPBTs by comparing patient and caregiver questionnaire scores with physician evaluations. Data are presented from 41 SPBTs. The TOSQ is a precise screening tool for identifying LEs in SPBTs based on the significant correlation (P < 0.05) that was found between parental scores and physician evaluations. Statistical testing proved that parents are a good source of information about child's health status, and that TOSQ accurately reflects the correlation between patient difficulties and quality of life. The TOSQ is the first described screening tool for identification of LEs designed specifically for SPBTs. It is simple to use and provides a valid, comprehensive and economic assessment followed by targeted treatment plan for each patient. By repeatedly using the TOSQ over the years, we can improve our ability to detect and give focused treatment to those who require assistance.

Female reproductive health after childhood, adolescent, and young adult cancers: guidelines for the assessment and management of female reproductive complications.

As more young female patients with cancer survive their primary disease, concerns about reproductive health related to primary therapy gain relevance. Cancer therapy can often affect reproductive organs, leading to impaired pubertal development, hormonal regulation, fertility, and sexual function, affecting quality of life. The Children's Oncology Group Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancer (COG-LTFU Guidelines) are evidence-based recommendations for screening and management of late effects of therapeutic exposures. The guidelines are updated every 2 years by a multidisciplinary panel based on current literature review and expert consensus. This review summarizes the current task force recommendations for the assessment and management of female reproductive complications after treatment for childhood, adolescent, and young adult cancers. Experimental pretreatment as well as post-treatment fertility preservation strategies, including barriers and ethical considerations, which are not included in the COG-LTFU Guidelines, are also discussed. Ongoing research will continue to inform COG-LTFU Guideline recommendations for follow-up care of female survivors of childhood cancer to improve their health and quality of life.

Surviving the cure: long term followup of hematopoietic cell transplant recipients

Advances in hematopoietic cell transplantation (HCT) have led to an increasing number of transplant survivors. However, long-term survival is challenged by late relapse, late complications and late non-relapse mortality, and HCT survivors need continued lifelong surveillance for screening, early detection and timely treatment of late complications such as secondary cancers, late infections and organ toxicity. Guidelines for screening and preventive practices for pediatric and adult survivors of autologous and allogeneic HCT were updated and published in 2012. However, several barriers to the care of HCT survivors and routine utilization of these guidelines in clinical practice exist. Examples include paucity of and challenges to conducting prospective randomized trials for screening and prevention of late complications, lack of resources to manage late effects at the level of transplant centers and community health care providers, and inadequate tools to facilitate care and followup of HCT survivors. We summarize the long-term followup guidelines in this review, discuss ways that providers can integrate and utilize them for the care of their patients, and identify areas for research that can inform and increase the utilization of screening and prevention guidelines in clinical practice.

The status of the cervical spine in preschool children with a history of congenital muscular torticollis

Background: Infants with congenital muscular torticollis are born with an asymmetric range of motion and a muscular imbalance in the cervical spine, as a result of a shortening or excessive contraction of the sternocleidomastoid muscle. Purpose: The study aimed to investigate passive range of motion (PROM) for rotation and lateral flexion, and muscle function of the cervical spine in children that had a history of CMT as infants. Study design: a prospective cohort study. Patient sample: 58 children at the age of 3.5 to 5 years that had been treated for CMT have infants participated in the study. Method: PROM was measured with protractors and muscle function was estimated with a modified Muscle Function Scale. Data from infancy were taken from earlier records. Result: PROM in rotation of the neck was mean 98.7&#176 and PROM in lateral flexion of the neck was mean 69.1&#176. Symmetric PROM of the neck was found in 74% of the children for rotation and in 88% of the children for lateral flexion. Multiple regression showed that gender and PROM in rotation as infants had a significant impact on asymmetric PROM. Forty-five percent of the children had some degree of muscular imbalance in the lateral flexors of the neck. Conclusion: Possible risk factors for later asymmetric PROM are: gender, birth weight, gestation week and PROM in rotation as infants. These factors ought to be taken into consideration when developing guidelines for long-term follow-up.

Yield of screening for long-term complications using the children's oncology group long-term follow-up guidelines.

The Children's Oncology Group Long-Term Follow-Up (COG-LTFU) Guidelines use consensus-based recommendations for exposure-driven, risk-based screening for early detection of long-term complications in childhood cancer survivors. However, the yield from these recommendations is not known. Survivors underwent COG-LTFU Guideline-directed screening. Yield was classified as negligible/negative (< 1%), intermediate (≥ 1% to < 10%), or high (≥ 10%). For long-term complications with high yield, logistic regression was used to identify subgroups more likely to screen positive. Over the course of 1,188 clinic visits, 370 childhood cancer survivors (53% male; 47% Hispanic; 69% leukemia/lymphoma survivors; median age at diagnosis, 11.1 years [range, 0.3 to 21.9 years]; time from diagnosis, 10.5 years [range, 5 to 55.8 years]) underwent 4,992 screening tests. High-yield tests included thyroid function (hypothyroidism, 10.1%), audiometry (hearing loss, 22.6%), dual-energy x-ray absorptiometry scans (low bone mineral density [BMD], 23.2%), serum ferritin (iron overload, 24.0%), and pulmonary function testing/chest x-ray (pulmonary dysfunction, 84.1%). Regression analysis failed to identify subgroups more likely to result in high screening yield, with the exception of low BMD (2.5-fold increased risk for males [P = .04]; 3.3-fold increased risk for nonobese survivors [P = .01]). Screening tests with negligible/negative (< 1%) yield included complete blood counts (therapy-related leukemia), dipstick urinalysis for proteinuria and serum blood urea nitrogen/creatinine (glomerular defects), microscopic urinalysis for hematuria (hemorrhagic cystitis, bladder cancer), ECG (anthracycline-related conduction disorder), and hepatitis B and HIV serology. Screening tests with a high yield are appropriate for risk groups targeted for screening by the COG-LTFU Guidelines. Elimination of screening tests with negligible/negative yield should be given consideration.

New health conditions identified at a regional childhood cancer survivor clinic visit

Specialty childhood cancer survivorship clinics have been established to screen for potential treatment-related effects. Given the limited empirical data regarding the merit of survivorship clinics, we assessed the frequencies of newly identified, therapy-related effects in survivors who attended Health, Education, Research, Outcomes for Survivors (HEROS) clinic at Yale during 2003-2009. A total of 213 survivors in remission, who were diagnosed with cancer at an age ≤21 years and were ≥3 years after cancer diagnosis, underwent screening based on cancer treatment exposures according to the children's oncology group long-term follow-up guidelines. The frequencies and associated factors of newly identified health conditions were determined. Odds ratios (OR) and their 95% confidence intervals were estimated using multivariate regression models with stepwise selection. Prior to the HEROS clinic visit, 49% of patients had at least one previously known late complication of therapy. After the visit, a total of 98 new health conditions were identified in 73 patients (34%). Newly identified complications in screened patients included pulmonary dysfunction (23%), endocrinopathy (19%), osteoporosis (17%), dyslipidemia (8%), neurologic impairment (4%), cardiovascular deficit (3%) and subsequent cancer (3%). Age at cancer diagnosis (OR = 1.06 [1.00-1.11]), chest irradiation (OR = 2.92 [1.58-5.40]), and history of ≥1 other treatment-related complication(s) (OR = 2.20 [1.18-4.07]) were associated with a higher likelihood of having new conditions identified. Risk-based screening at a specialty childhood cancer survivor clinic detected a substantial number of previously unrecognized, treatment-related health complications in a group of survivors already receiving regular medical care elsewhere.

Male reproductive health after childhood, adolescent, and young adult cancers: a report from the Children's Oncology Group.

The majority of children, adolescents, and young adults diagnosed with cancer will become long-term survivors. Although cancer therapy is associated with many adverse effects, one of the primary concerns of young male cancer survivors is reproductive health. Future fertility is often the focus of concern; however, it must be recognized that all aspects of male health, including pubertal development, testosterone production, and sexual function, can be impaired by cancer therapy. Although pretreatment strategies to preserve reproductive health have been beneficial to some male patients, many survivors remain at risk for long-term reproductive complications. Understanding risk factors and monitoring the reproductive health of young male survivors are important aspects of follow-up care. The Children's Oncology Group Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancer (COG-LTFU Guidelines) were created by the COG to provide recommendations for follow-up care of survivors at risk for long-term complications. The male health task force of the COG-LTFU Guidelines, composed of pediatric oncologists, endocrinologists, nurse practitioners, a urologist, and a radiation oncologist, is responsible for updating the COG-LTFU Guidelines every 2 years based on literature review and expert consensus. This review summarizes current task force recommendations for the assessment and management of male reproductive complications after treatment for childhood, adolescent, and young adult cancers. Issues related to male health that are being investigated, but currently not included in the COG-LTFU Guidelines, are also discussed. Ongoing investigation will inform future COG-LTFU Guideline recommendations for follow-up care to improve health and quality of life for male survivors.

A national survey of general internists' preferences and knowledge gaps regarding the care of childhood cancer survivors.

9586 Background: Although most childhood cancer survivors (CCS) report obtaining health care in the community, primary care physicians’ views and knowledge regarding the long-term follow-up (LTFU) care of CCS are largely unknown. Methods: Surveys were mailed to a random sample of 1,907 general internists under age 65 years from the American Medical Association Physician Masterfile in November 2011. A second mailing to non-responders is ongoing. Results: 892 (47%) physicians have responded. Respondents have practiced a median of 10 years (range: 3-20), and see a median of 70 patients/week (range: 40-100). 46% are in solo/group practice, 17% in multi-specialty practice, and 14% in academic practice. In the last five years, 53% have seen at least one CCS, 71% of whom have never received a treatment summary. 85% prefer to care for CCS in consultation with a cancer center based physician. A vignette of a 29-year-old female treated for Hodgkin lymphoma with mantle radiation at age 16 was provided and participants were asked a series of questions regarding monitoring for late effects. The percentage of responses that were concordant with available LTFU Surveillance Guidelines were: breast cancer, 29%; cardiac, 15%; thyroid, 77%; and all three recommendations, only 5%. By logistic regression, greater likelihood of concordance with at least one surveillance recommendation was associated with being female (OR=2.0 95% CI 1.3-3.1), seeing more patients/week (OR=1.4 per SD increase, 95% CI 1.1-1.7) and more years in practice (OR=1.3 per SD increase, 95% CI 1.0-1.6). The two modalities felt to be most useful for independent care of CCS by internists were access to LTFU guidelines and receiving a patient-specific care plan from the cancer center. Conclusions: Although the majority of internists are willing to follow CCS, they appear unfamiliar with the available LTFU guidelines and prefer to care for patients in collaboration with a cancer center based physician.

Physician Preferences and Knowledge Regarding the Care of Childhood Cancer Survivors in Japan: A Mailed Survey of the Japanese Society of Pediatric Oncology

Japanese physicians' attitudes regarding the health-care needs of young adult childhood cancer survivors (CCSs) are not well described. Thus, we examined the self-reported preferences and knowledge of pediatric oncologists and surgeons. A mailed survey was sent to 858 physician members of the Japanese Society of Pediatric Oncology. We compared the responses of pediatric oncologists and pediatric surgeons. The pediatric oncologists' response rate was 56% (300 out of 533) and that of pediatric surgeons 32% (105 out of 325). The median age of respondents was 46 and 48 years, respectively; 79 and 84% were men. When comfort levels in caring for CCSs were described (i.e. 1 = very uncomfortable; 7 = very comfortable), the mean levels were 4.4 and 3.8 with CCSs ≤ 21 years, 3.6 and 3.6 with 21 years < CCSs ≤ 30 years, and 2.8 and 3.3 with CCSs > 30 years, respectively. In clinical vignette questions, 62% of the pediatric oncologists and 43% of the surgeons answered three or more questions appropriately. Pediatric surgeons reported significantly lower familiarity with long-term follow-up guidelines than pediatric oncologists. Most pediatric oncologists and many surgeons conducted truth-telling of cancer diagnosis to adult CCSs now. They thought that the most important issues are an original long-term follow-up guideline suitable for the Japanese situation and collaborations with adult-based general physicians. Many Japanese pediatric oncologists are uncomfortable with caring for survivors as they age and have suboptimal knowledge regarding late effects. The change in truth-telling situation and preference for collaboration with adult-based physicians was demonstrated also in Japan.

Consultation with the Specialist: Thyroid Nodules

Based on strong research evidence, thyroid nodules in children and teenagers are more likely to be malignant than in adults. Based on strong research evidence, a history of ionizing radiation to the head or neck is an independent risk factor for the development of thyroid malignancies. There is strong research evidence, including a recent meta-analysis, supporting the use of fine-needle aspiration biopsy in the evaluation of all pediatric and adolescent patients presenting with a thyroid nodule. The surgical management and postoperative care of pediatric and adolescent patients who have well-differentiated thyroid carcinomas remains controversial, because the rarity of the disease limits the ability to conduct randomized, prospective research studies. Numerous studies have demonstrated that, despite presenting with more advanced disease, pediatric and adolescent patients with thyroid carcinoma have a higher survival rate than adults. The American Thyroid Association has issued strong evidence-based recommendations for the management of medullary thyroid carcinoma, including RET mutation testing and early prophylactic total thyroidectomy in children with high-risk mutations.

Bilateral refractory frozen shoulders treated with conservative and surgical treatments—a case report of long-term follow-up

Keywords Frozenshoulder.Physiotherapy.Arthroscopiccapsularrelease.Casereport.Long-termfollow-upIntroductionShoulder stiffness is a major cause of shoulder disability andpain. It was first described in the late 19th century [1, 2].The term frozen shoulder was first described by Codman in1934, who stated the common features of slow onset painnear the insertion of the deltoid, inability to sleep on theaffected side, painful and restricted elevation and externalrotation, and a normal radiological appearance [3]. Clinicalfeatures of idiopathic frozen shoulder are classically charac-terized by three stages: freezing, frozen, and thawing phases[4]. Their characteristic clinical feature is decreasing motionwith pain, severely restricted motion, and recovering fromstiffness, respectively. The estimated prevalence of frozenshoulder is 2–5% in the general population [5, 6]. Patientswith frozen shoulder are observed commonly in their 40s to70s and predominately in females [7, 8]. In addition,20–30% of patients develop stiffness in the contralateralshoulders [7]. Though the natural history of frozen shoulderis not well understood, idiopathic frozen shoulder is consid-ered to be a self-limited disease [3, 9]. Normally, quite a fewpatients respond well with conservative treatments such assteroid injections and physiotherapy [10]. However, somepatients demonstrate little or no improvement or mildimprovement with various degrees of limited range ofmotion. In the recalcitrant cases, surgical intervention, suchas arthroscopic pan-capsular release [11], is indicated.We have experienced a case of bilateral idiopathic frozenshoulders which underwent arthroscopic pan-capsular releaseon one side and conservative treatment, which is mostlyperiodical physiotherapy, on the other side for 5 years. Thepurpose of this study is to report range of motion (ROM)recovery over time of this long-term follow-up case and toprovide guidelines for surgeon’s decision making.Case reportHistory A 56-year-old woman in good general health suf-fered from severe left shoulder pain, which was her

Long-Term Follow-up and Management Guidelines in Pediatric Patients After Allogenic Hematopoietic Stem Cell Transplantation

Over the past 50 years there has been considerable progress and success in the field of allogeneic hematopoietic stem cell transplant (HSCT) in children. In addition there has been significant improvement in transplant outcomes for both malignant and nonmalignant indications. These improved outcomes have resulted in many long-term survivors who are experiencing substantial long-term morbidities. There are limited data examining the long-term complications of transplant on the various organs. This issue is complicated by the fact that children receive their transplant at different stages of their growth and development (ie, infant, toddler, child, adolescent, and young adult). Each of these developmental stages has different sensitivities to treatment and can result in different sets of complications. We summarize the long-term side effects of allogeneic HSCT in children.

Human papillomavirus vaccination and the primary prevention of cancer: implications for survivors of childhood cancer.

Effective vaccination is now available to prevent human papillomavirus (HPV), the most common sexually transmitted infection and the cause of cervical cancer, the second most common cancer among women worldwide. HPV vaccine uptake is particularly important for females surviving cancer, who are at high risk for HPV-related complication due to the direct and indirect effects of cancer therapy. Thus, Version 3.0 of the Children's Oncology Group Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent and Young Adult Cancer recommends HPV vaccination for all eligible females surviving childhood cancer. Because this vaccine was only FDA approved in 2006, little is known about the complexity of vaccination uptake among those surviving childhood cancer. This chapter describes HPV vaccination and its usefulness in survivors of childhood cancer, provides a rationale for describing survivors as being at increased risk for HPV-related complication, identifies factors that are predictive of HPV vaccination, and discusses the utilization of these predictors in designing strategies to promote adherence to the HPV vaccination recommendations among survivors.

Endocrine Health Problems Detected in 519 Patients Evaluated in a Pediatric Cancer Survivor Program

Many pediatric cancer survivors have endocrine conditions. Surveillance for late effects is recommended by national guidelines. Endocrine surveillance is recommended after alkylating agents, steroids, methotrexate, and radiation. The objective of the study was to describe the endocrine outcomes in patients followed up in a program that uses national screening guidelines. The design of the study was a medical records review. The study was conducted in the Comprehensive Cancer Survivor Program, an academic pediatric oncology program. The study included 519 pediatric and young adult survivors of noncentral nervous system childhood malignancies between January 1, 2001, and December 15, 2005. Patients were evaluated with history, physical examinations, and evaluations recommended in the Children's Oncology Group's Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent and Young Adult Cancers. The frequency and types of endocrine conditions were measured. Four hundred eighty endocrine conditions were observed in 299 survivors (57.6% of survivors). The most common types of endocrine conditions were problems with weight and gonadal function. In a Cox regression model, stem cell transplant, radiation, and older age at cancer diagnosis were associated with higher hazard of an endocrine condition. Radiation, stem cell transplant, and sarcoma diagnosis were associated with growth problems. Endocrine disorders were common after pediatric cancers. Endocrinologists should be aware of national guidelines, anticipate referral of pediatric cancer survivors, and participate in further research to optimize screening for and treatment of endocrine effects of cancer therapy.

Long-term health impacts of hematopoietic stem cell transplantation inform recommendations for follow-up

Advances in transplantation techniques and supportive care strategies have resulted in a significant improvement in survival of those who have undergone treatment. However, hematopoietic stem cell transplantation (HSCT) survivors are at risk of developing long-term complications, such as endocrinopathies, musculoskeletal disorders, cardiopulmonary compromise and subsequent malignancies. These complications have a direct impact on the morbidity and mortality experienced by HSCT survivors. Two-thirds of HSCT survivors develop at least one chronic health condition; while a fifth develop severe or life-threatening conditions. HSCT patients who have survived for at least 5 years post-transplantation are at a fourfold to ninefold increased risk of late mortality for as long as 30 years from HSCT, producing an estimated 30% lower life expectancy compared with the general population. The high burden of morbidity experienced by HSCT survivors makes it critically important that there is standardized follow-up of HSCT survivors at high risk for post-HSCT complications. The Center for International Blood and Marrow Transplant Research/European Group for Blood and Marrow Transplantation/American Society for Blood and Marrow Transplantation and the Children’s Oncology Group long-term follow-up guidelines offer such standardized care. Future steps include wider dissemination and refinement of these guidelines.

Physician preferences and knowledge gaps regarding the care of childhood cancer survivors: A survey of the American Academy of Family Physicians (AAFP).

9128 Background: Little is known about primary care physicians’ attitudes and knowledge regarding the health and long term follow-up (LTFU) of childhood cancer survivors (CCS). We sought to obtain family physicians’ (FPs) self-reported preferences and knowledge regarding this population. Methods: Following a pre-notification letter, surveys with a $2 bill were mailed to 1520 physicians from the AAFP membership directory in November 2010. A second mailing to non-responders is ongoing. Results: To date, 529 FPs have responded (35% response rate). Respondents have practiced a median of 25 years and see a median of 80 patients/week. In the last five years, 63% had seen at least one CCS in their practice; about half (54%) report almost never receiving a treatment summary. Among 3 specific cancer types, respondents’ discomfort in caring for CCS (1 = very uncomfortable; 7 = very comfortable) was greatest for osteosarcoma survivors (3.2 ± 1.7), less with ALL survivors (3.3 ± 1.7), and least with Hodgkin lymphoma (HL) survivors (mean ± SD 3.6 ± 1.7). The majority (82%) prefer to care for CCS in consultation with a cancer center based physician and/or LTFU clinic. A vignette of a 29-year-old female treated for HL with mantle radiation at age 16 was provided, participants were asked a series of follow-up monitoring questions. Concordance of responses to the Children’s Oncology Group LTFU Guidelines was: breast cancer surveillance, 18%; cardiac surveillance; 10%, and thyroid surveillance, 71%. Only 3% were concordant with all three of these questions. Concordance with breast cancer and cardiac questions was associated with reported familiarity with guidelines (OR=3.49, 95% CI 1.79-6.78; OR=3.73, 95% CI 1.73-8.04, respectively). In describing what would be most useful to care for CCS (1=not at all useful; 5=very useful), among 11 options, FPs reported the most preferred were access to LTFU guidelines (4.7 ± 0.6) and a patient-specific care plan (4.7 ± 0.6). Conclusions: While the majority of FPs are willing to follow CCS, they express some discomfort with this care, appear unfamiliar with the available LTFU guidelines and prefer to follow patients in collaboration with a cancer center.

Physician preferences and knowledge regarding the care of childhood cancer survivors in Japan: A mailed survey of the Japanese Society of Pediatric Oncology.

e19522 Background: Japanese physicians’ attitudes regarding the health care needs of childhood cancer survivors (CCSs) are not well described. Thus we examined the self-reported preferences and knowledge of pediatric oncologists and surgeons concerning this population. Methods: A mailed survey was sent to 858 physician members of the Japanese Society of Pediatric Oncology in October 2010 according to the methods of Henderson et al (JCO 28 (5):878, 2010). Results: A total of 405 surveys were returned (47% response rate); of which 300/533 pediatric oncologists and 105/325 and surgeons responded, respectively. Respondents’ median age was 46 and 48 years, respectively; 79% and 84% men. There were no differences between physicians excluding living area distributions and educational opportunities of late effects. Less than one third of respondents (31%) report referring survivors to other physicians. When comfort levels in caring for CCSs were described (1 = very uncomfortable; 7 = very comfortable), physicians were most comfortable with CCS <= 21years (4.4 ± 1.3 and 3.8±1.4), less comfortable with CCSs > 21 years but < 30 years old (3.6 ± 1.4 and 3.6 ± 1.4), and least comfortable with CCS >30 years (2.8 ± 1.5 and 3.3 ± 1.6). Familiarity with long-term follow-up guidelines was quite lower in surgeons (2.8 ± 1.4 vs 1.5 ± 1.4). In response to a clinical vignette of a 25 year old woman treated at 1 year with prophylactic cranial radiation (24 Gy), 62 % of pediatric oncologists and 43% of surgeons answered 3 or more questions regarding follow-up frequency, Hepatitis C surveillance, and late effects of cranial radiation in concordance with Japanese recommendations. Logistic regression analysis limited to pediatric oncologists showed learning experience (OR= 1.75; 95% CI, 1.05 to 2.93); practicing in a children’s hospital (OR 5.11; 95% CI, 1.15 to 22.8); and practicing in a general hospital (OR, 0.55; 95% CI, 0.32 to 0.95) were associated with answering three or more questions correctly. Conclusions: Preferences and knowledge with regard to long-term follow-up care of CCSs differ between pediatric oncologists and surgeons in Japan; pediatric oncologists appear to be more comfortable.

Characteristics of childhood cancer survivors who attend long-term follow-up (LTFU) clinic.

9566 Background: Although the Children’s Oncology Group developed LTFU guidelines for childhood cancer survivors, the majority of adult survivors do not receive risk-based care through a LTFU program. This study aimed to identify characteristics of pediatric cancer survivors who return to a LTFU Clinic for care compared with patients who do not. Methods: Chart review of patients eligible to be seen in the LTFU Clinic who completed treatment between 1/1990 and 11/2010. Patient characteristics (demographics, school functioning, high-risk behaviors such as using drugs, alcohol, cigarettes) and treatment characteristics (diagnosis, treatment) were abstracted from medical records. Review of 137 charts so far revealed that eligible patients ranged in age from 6 to 37 years (M = 22.5, SD = 6.8), were 52.6% male, 88.3% Caucasian, and completed treatment about 13 years earlier. Point biserial correlations and Chi-square analyses were used to determine associations between patient and treatment characteristics and LTFU attendance. Results: 46.7% of patients had attended LTFU Clinic within 2 years of their last recommended follow-up. Current age was significantly inversely associated with current attendance, rpb = -.47, p < .001. Similarly, patients aged >18 were less likely to be current compared with patients <18, χ2(1) = 30.45, p < .001. There were no significant differences based on treatment received (surgery, radiation, chemotherapy), risk status for late effects, or documented late effects. Patients were less likely to be current if they had a documented psychiatric disorder (e.g., depression, anxiety), χ2(1) = 5.79, p = .016 or had reported past or ongoing drug use, χ2(1) = 4.68, p = .031. For patients >18 at last visit, there was a non-significant trend suggesting those who were married were more likely to be current, χ2(1) = 2.83, p = .09. Conclusions: Adult survivors of childhood cancer are less likely than younger counterparts to participate in recommended LTFU at a pediatric institution. Significant factors associated with current attendance included age and psychosocial issues, such as documented psychiatric problems and drug use. Patients like these may require additional monitoring to promote engagement in LTFU care.