Oncology Group Long-term Follow-up Research Articles

Prevalence of carotid ultrasound screening in survivors of childhood cancer: A report from the Childhood Cancer Survivor Study.

Many childhood cancer survivors are at risk for cardiovascular disease and stroke. The North American Children's Oncology Group long-term follow-up guidelines recommend carotid ultrasound in cancer survivors 10 years after neck radiation therapy (RT) ≥40 Gy. The use of carotid ultrasound in this population has not been described. Survivors of childhood cancer diagnosed 1970-1999 (N=8693) and siblings (N=1989) enrolled in the Childhood Cancer Survivor Study were asked if they had ever had a carotid ultrasound. Prevalence of carotid ultrasound was evaluated. Prevalence ratios (PR) and 95% confidence intervals (CIs) were evaluated in multivariate Poisson regression models. Among participants with no reported cardiovascular condition, prevalence of carotid ultrasound among survivors with RT≥40 Gy to the neck (N=172) was 29.7% (95% CI, 22.5-36.8), significantly higher than those with <40 Gy (prevalence 10.7%; 95% CI, 9.9%-11.4%). Siblings without a cardiovascular condition (N=1621) had the lowest prevalence of carotid ultrasound (4.7%; 95% CI, 3.6%-5.7%). In a multivariable models among survivors with no reported cardiovascular condition and RT≥40 Gy to the neck, those who were over age 50 (vs. 18-49) at follow-up (PR=1.82; 95% CI, 1.09-3.05), with a history of seeing a cancer specialist in the last 2 years (PR=2.58; 95% CI, 1.53-4.33), or having a colonoscopy (PR=2.02; 95% CI, 1.17-3.48) or echocardiogram (PR=6.42; 95% CI, 1.54-26.85) were more likely to have had a carotid ultrasound. Many survivors do not undergo carotid ultrasound despite meeting existing guidelines. Health care delivery features such as having seen a cancer specialist or having other testing are relevant.

Sexual and Reproductive Health Care after Gonadotoxic Treatment in Females at a Tertiary Pediatric Hospital

Study ObjectivesRecommendations from the Children's Oncology Group Long-Term Follow-Up (COG-LTFU) Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancer emphasize the importance of reproductive health care, yet little is known regarding adherence to these recommendations and non-fertility-related sexual and reproductive health (SRH) outcomes. MethodsFollow-up of outcomes on the basis of the COG-LTFU guidelines was assessed in female patients who underwent fertility preservation consultation before gonadotoxic therapy between 2016 and 2022 at a single institution and were at least 6 months from treatment completion. ResultsWe included 140 patients, with a mean time of 2.7 years from treatment completion. Eighty-six patients were 12 years old or older, of whom sexual activity was recorded in 59 (68.7%), and 12 of 31 (38.7%) sexually active patients underwent sexual function assessment. The 57 (66.3%) patients at high risk of premature ovarian insufficiency (POI) at diagnosis were more likely than minimal-risk counterparts (29, 33.7%) to have abnormal uterine bleeding (42.1% vs 17.2%, P = .03), to be diagnosed with POI (29.8% vs 0%, P = .01), and to have sexual activity recorded (77.2% vs 51.7%, P = .03). Of 17 patients with POI, 82.4% were on hormone replacement therapy, and 58.8% had undergone bone mineral density testing. ConclusionThis study adds to the limited literature regarding non-fertility-related SRH outcomes after gonadotoxic therapy and illustrates opportunities to improve adherence to the COG-LTFU guidelines. Increased attention to SRH guidelines may increase detection and treatment of SRH conditions, improving the health and quality of life of female cancer survivors.

An Evidence Review of the Long-Term Consequences Associated with Components of the CHOP Chemotherapy Regimen in Transplant Recipients

Introduction: Epstein-Barr virus-driven post-transplant lymphoproliferative disease (EBV + PTLD) can be an aggressive, often deadly disease without any approved treatments. Current available treatments for EBV + PTLD may include cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). However, the long-term consequences of CHOP are poorly understood in immunocompromised transplant patients with cancer who may have different outcomes than immunocompetent cancer patients. This study reviewed and described the evidence for the long-term consequences associated with components of CHOP in transplant recipients.Methods: Potential long-term consequences of the components of CHOP were identified from the Children's Oncology Group Long-Term Follow-Up (COG LTFU) Guidelines. Abstracts were screened and eligibility was based on reporting data for the identified COG LTFU long-term consequences along with pre-specified criteria (English, systematic review, randomized controlled trial n>100, observation study n>100, case series n>20). Relevant studies that met the criteria were extracted and synthesized; of these, studies were selected if they evaluated patients who received any type of transplantation as part of their primary cancer treatment.Results: A total of 7 studies met the pre-specified selection criteria, all of which evaluated patients with hematopoietic stem cell transplantation (HCT) and none assessed solid organ transplant (SOT). None of the studies focused specifically on the CHOP regimen or EBV + PTLD. Long-term consequences of alkylating agents (eg, cyclophosphamide) and corticosteroids as primary treatment reported in these HCT studies included: hormone deficiencies and infertility (n=4 studies), osteonecrosis (n=2), and health status and quality of life (QoL; n=1).Results from three studies suggested that cancer survivors who received alkylating agents experienced hormone deficiencies and those with a HCT had a high risk. One quantified this by showing that, compared with cancer survivors without a history of HCT (CS), cancer survivors with a history of HCT (CS-HCT) and a history of total body irradiation had significantly impaired follicle stimulating hormone (40.42 vs 9.39 mIU/ml, P<0.001), Estradiol (15.09 vs 25.13 pg/ml, P=0.04), Inhibin B (10.61 vs 32.92 pg/ml, P=0.003), anti-Müllerian hormone (0.01 vs 1.28 ng/ml, P<0.001), antral follicle count (0.71 vs 17.78, P<0.001) and ovarian volume (1.82 vs 8.21 ml, P<0.001). In one study on the risk of osteonecrosis, the CS-HCT group had a significantly increased risk of developing osteonecrosis compared to the CS group treated with chemotherapy (6.8% vs 1.4%, respectively); cumulative incidence of osteonecrosis was 3.8% in the CS group for a steroid dose >5,835 mg/m 2 and 23.8% in the CS-HCT group for a post-transplant steroid dose >2,055 mg/m 2; and patients developed symptomatic osteonecrosis within a median of 2.4 years in the CS group with chemotherapy and 0.9 years after the first transplant in the CS-HCT group. A second study showed the rate ratio (RR) of osteonecrosis compared with a sibling comparison group was highest among the CS-HCT for acute lymphoblastic leukemia, acute myelogenous leukemia, and chronic myelogenous leukemia (RR = 26.9, 66.5, and 93.1, respectively; P<0.001 for all). One study reported that childhood acute leukemia survivors treated with HCT with preparative regimen with either busulfan-cyclophosphamide or total body irradiation/cyclophosphamide had a significantly lower QoL short-form (SF)-36 mental and physical composite scores in both treatment groups compared with norms.Conclusions: Since only a small number of studies (7) of long-term consequences in transplant recipients were identified and none were seen in patients with EBV + PTLD or in SOT recipients, more research is needed to evaluate adverse consequences of CHOP or its components in EBV + PTLD, especially in SOT patients where no studies were found. Results from this review suggest that immunocompromised HCT recipients who were cancer survivors are significantly more impaired by long-term consequences (hormone deficiencies and infertility, osteonecrosis, and QoL) of alkylating agents (eg, cyclophosphamide) and corticosteroids as primary treatment compared with other cancer survivors without HCT. DisclosuresWatson: Atara Biotherapeutics: Current Employment, Current holder of individual stocks in a privately-held company. Gadikota: Maple Health Group: Current Employment. Barlev: Atara Biotherapeutics: Current Employment. Beckerman: Maple Health Group: Current Employment.

Quantification of Long-Term Consequences Associated with Components of the CHOP Chemotherapy Regimen

Introduction: A common chemotherapy regimen for Epstein-Barr virus-driven post-transplant lymphoproliferative disease (EBV + PTLD) following solid organ transplants is cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). Long-term adverse consequences of CHOP, particularly the incidence, timing, and risk factors associated with these events, in any cancer survivor remain poorly understood. In this study, we review the evidence to determine how often long-term consequences associated with the components of CHOP occur.Methods: Potential long-term consequences of CHOP components were identified from the Children's Oncology Group Long-Term Follow-Up (COG LTFU) Guidelines. Abstracts were screened and eligibility was based on reporting data for the identified COG LTFU long-term consequences along with pre-specified criteria (English, systematic review, randomized controlled trial n>100, observation study n>100, case series n>20). Studies that met the inclusion criteria were extracted and synthesized. Quantification of late effects evaluated in >3 studies were reported.Results: Long-term consequences in the 45 studies that met the pre-specified criteria included cardiac toxicity, hormone deficiencies/infertility, secondary leukemia, osteonecrosis (ON), and urotoxicity/bladder cancer. Although none of the studies focused specifically on the CHOP regimen, 30%, 23%, and 15% evaluated alkylating agents (eg, cyclophosphamide), anthracyclines (eg, doxorubicin), and corticosteroids (eg, prednisone), respectively. Time to onset from treatment was as early as 1 year for cardiac toxicity, <5 for infertility, 2 for ON, 3 for secondary leukemia, and 5 for bladder cancer. Longer follow-up times were associated with higher percentages of long-term consequences. For example, cardiac toxicity and hormone deficiencies/infertility affected >20% of patients, and secondary leukemia, ON, urotoxicity/bladder malignancy affected 10-20% of patients (Table 1). A wide range in the incidence and timing of these late effects was observed, likely due to variation in the treatment regimens, follow-up time, and event definition.The synthesized evidence supports that CHOP components increased the risk of long-term consequences in a dose-dependent manner. Cardiac toxicity risk was elevated even at anthracycline doses of <150 mg/m 2 (traditionally considered a ‘safe’ dose range). Hazard ratios (HRs) for heart failure at doses of ≤300 to <400 mg/m 2 were 4.33 and 13.19 for daunorubicin and doxorubicin, respectively. Studies also reported significantly elevated risk of cardiac toxicity in patients with lymphoma treated with anthracyclines (eg, HR of up to 12.2) compared with the sibling cohort. Patients <5 years of age vs ≥5 years of age at exposure had a significantly higher risk of cardiac toxicity (HR of 1.89). Patients exposed to cumulative doses of cyclophosphamide ≥6 g/m 2 had significant reproductive risks. The risk of early menopause was shown to be dose dependent and as much as 27-fold higher in patients treated with both radiation below the diaphragm and alkylating agent chemotherapy. Patients exposed to high-dose cyclophosphamide (>7.5 g/m 2) were at statistically significantly higher risk (odds ratio of 12.0) for diminished ovarian reserve as measured by their Anti-Müllerian hormone level. One study reported 3.8- and 3.2-fold increases in risk of ovarian failure in patients who had been diagnosed with Hodgkin's lymphoma and Non-Hodgkin's lymphoma, respectively. High-doses of anthracyclines and alkylating agents were associated with up to 16-fold increases in risk of secondary leukemia. The risk of bladder cancer significantly increased with increasing dose of cyclophosphamide, with a 6- and 14.5-fold increased risk at cumulative doses of 20‒49 g and ≥50 g, respectively. Intensive corticosteroid therapy was associated with significant risk of ON, with one study showing cancer survivors had a 6.2 times higher likelihood of ON as compared to their sibling comparison group.Conclusions: Patients exposed to components of CHOP have a dose-dependent risk of cardiac toxicity, infertility, secondary leukemia, ON, and bladder cancer that are often significant, impacted a high percentage of patients, and occurred as early as 1 year after treatment. Safe and effective PTLD treatments that potentially avoid these long-term consequences are urgently needed. [Display omitted] DisclosuresWatson: Atara Biotherapeutics: Current Employment, Current holder of individual stocks in a privately-held company. Gadikota: Maple Health Group: Current Employment. Barlev: Atara Biotherapeutics: Current Employment. Beckerman: Maple Health Group: Current Employment.

Utilization of Cardiac Surveillance in Pediatric Blood Cancer Survivors Who Received Anthracycline-Based Therapy Differs By Age: A Claims-Based Analysis

Background: The Children's Oncology Group Long-Term Follow-up Guidelines recommend surveillance for late effects in pediatric cancer survivors based on therapeutic exposures. In particular, the Guidelines recommend an echocardiogram, or comparable imaging, every 2 to 5 years to evaluate cardiac function in survivors exposed to anthracycline chemotherapy. However, little is known about the real-world utilization of cardiac surveillance tests following the completion of cancer therapy.Objective: This study fills this gap by describing the proportion of anthracycline-treated survivors of pediatric cancer who received surveillance for cardiac function following the completion of their cancer therapy.Method: We developed an algorithm to identify a cohort of pediatric cancer survivors using the IBM MarketScan ® Commercial Claims and Encounters Database (a nationwide private insurance enrollment and claims database). The cohort for inclusion was enrollees who (1) received anthracycline for blood cancer (leukemia or lymphoma); (2) aged ≤21 years at cancer diagnosis; (3) completed all cancer therapy between 2009 and 2018; and (4) remained continuously insured for at least one year post-therapy. Outcomes assessed included the receipt of: (1) echocardiogram, (2) cardiac magnetic resonance imaging (MRI), (3) multiple gate acquisition (MUGA) scan, and (4) any of the aforementioned cardiac surveillance tests over the 5-year period after the completion of all cancer therapy. The Kaplan-Meier (K-M) method was used to estimate the cumulative incidence of an event post-therapy, where the event was defined as the initial healthcare claim for a cardiac surveillance test. Individuals were censored if they had not received a test by study termination or were lost to follow-up at any time during the 5 years post-therapy. Multivariate Cox proportional hazard models were estimated to identify the demographic and cancer-related factors strongly associated with the initial test receipt.Results: Among 1,914 eligible blood cancer survivors, 259 (13.5%) survivors received a hematopoietic stem cell transplantation (HSCT; Table 1). The K-M estimated probability of receiving a cardiac surveillance test by 5 years post-therapy was 61.0% (95% Confidence Interval [CI]: 57.2% to 64.7%), with the median time to the initial test being 2.6 years (95% CI: 2.2 to 3.1 years) from therapy completion. The vast majority of cardiac surveillance test users underwent an echocardiogram (n=850; versus only 10 who had a cardiac MRI, and 14 who had a MUGA scan) by the end of their follow-up period.The proportion of survivors who had an initial cardiac test increased over time but varied by age at cancer therapy completion and the receipt of HSCT. The K-M estimated probability of receiving an initial test by 5 years post-therapy was: 86.0% (95% CI: 77.3% to 91.6%) for children (ages ≤11 years), 85.0% (95% CI: 75.4% to 91.1%) for adolescents (ages 12-17 years), and 36.8% (95% CI: 32.6% to 41.0%) for young adults (ages 18-28 years; Figure 1). Multivariate Cox models showed that compared with children, adolescents were more likely to receive an initial cardiac test (Hazard Ratio [HR] = 1.3; 95% CI: 1.1 to 1.5), while young adults were less likely to receive a test (HR = 0.4; 95% CI: 0.3 to 0.5). In addition, survivors who received a HSCT were more likely than those who did not to complete an initial cardiac test (HR=1.8; 95% CI: 1.5 to 2.2).Conclusions: This nationwide, claims data-based study showed that a substantial proportion of anthracycline-exposed survivors of blood cancers had not completed a cardiac surveillance test within 5 years post-therapy. Within this high-risk population, young adults were significantly less likely to receive surveillance testing for the prevention and early detection of cardiac dysfunction. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Adherence to Children’s Oncology Group Long-Term Follow-up Guidelines among high-risk adolescent and young adult cancer survivors

Adherence to Children’s Oncology Group Long-Term Follow-up Guidelines among high-risk adolescent and young adult cancer survivors

"There Is No Before Cancer… There Is Only Cancer." Perceived Late Effects of Pediatric Cancer on Survivors.

Although "late effects" connotes experiencing effects later in life, they can emerge immediately after active treatment. The effects that survivors experience have been reported but rarely from the point of view of the survivors regarding their life after treatment. To examine the perceived late effects of pediatric cancer on survivors and their self-identified primary support persons in order to understand the multifaceted nature of living after a pediatric cancer diagnosis. Using a pragmatic interpretive phenomenology approach, 10 survivors of pediatric cancer (aged 21-28 years) and 9 of their support persons (aged 23-73 years) participated, completing background questionnaires and semistructured, one-on-one interviews. Interview transcripts were analyzed thematically. Both survivors and support persons acknowledged that survivors experienced negative physical and cognitive health outcomes that require follow-up care. Survivors acknowledged that their cancer experience and residual effects have changed the trajectory of their lives. Research on young adult survivors of pediatric cancer and the residual/late effects and emotional outcomes they experience is warranted. Longitudinal research can aid in understanding how effects develop or worsen over time. The findings of this study support The Children's Oncology Group Long-term Follow-up Guidelines for practitioners. As the frontline caring for these individuals and families, nurses' involvement in transitional care out of treatment is necessary. Continued involvement and understanding of long-term pediatric cancer survivorship for nurses are also imperative for continuity for survivors and families.

Risk factors and surveillance for reduced bone mineral density in pediatric cancer survivors.

Pediatric cancer survivors are at increased risk of developing low bone mineral density (BMD) due to cancer treatment. This study assessed the yield of screening for low BMD in pediatric-aged cancer survivors as per the Children's Oncology Group Long-Term Follow-Up (COG-LTFU) Guidelines, which recommend screening survivors who received steroids, methotrexate, or hematopoietic cell transplant (HCT). This is a retrospective cohort study of 475 pediatric blood cancer and noncentral nervous system solid tumor survivors screened for low BMD with dual-energy X-ray absorptiometry (DXA) as per the COG-LTFU Guidelines from 2003 to 2010. Risk factors for low BMD (DXA Z-score ≤-2) were evaluated by univariate and multivariate analysis. The mean DXA Z-score was -0.1 for both whole body and lumbar spine measurements. Among at-risk survivors, 8.2% (39/475) had low BMD. Multivariate analysis of survivors with low BMD showed significant association with male gender (odds ratio [OR] 3.4, 95% confidence interval [CI], 1.3-9.0), exposure to total body irradiation (TBI), cranial, or craniospinal radiation (OR 5.2, 95% CI, 1.8-14.9), and gonadal dysfunction (OR 4.3, 95% CI, 1.4-13.0). Methotrexate exposure was not significantly associated with low BMD. Survivors receiving HCT had a reduced risk of low BMD (OR 0.2, 95% CI, 0.1-0.9). The highest risk factors for low BMD were male gender, exposure to TBI, cranial, or craniospinal radiation, and gonadal dysfunction. Survivors receiving methotrexate or HCT therapy have the lowest risk for low BMD among those screened. Future studies should investigate risk of low BMD for survivors receiving HCT without radiation exposure.

Cost-effectiveness of the children's oncology group long-term follow-up screening guidelines for childhood cancer survivors at risk for treatment-related heart failure.

Childhood cancer survivors treated with anthracyclines are at high risk for asymptomatic left ventricular dysfunction (ALVD), subsequent heart failure, and death. The consensus-based Children's Oncology Group (COG) Long-Term Follow-up Guidelines recommend lifetime echocardiographic screening for ALVD. To evaluate the efficacy and cost-effectiveness of the COG guidelines and to identify more cost-effective screening strategies. Simulation of life histories using Markov health states. Childhood Cancer Survivor Study; published literature. Childhood cancer survivors. Lifetime. Societal. Echocardiographic screening followed by angiotensin-converting enzyme (ACE) inhibitor and β-blocker therapies after ALVD diagnosis. Quality-adjusted life-years (QALYs), costs, incremental cost-effectiveness ratios (ICERs) in dollars per QALY, and cumulative incidence of heart failure. The COG guidelines versus no screening have an ICER of $61 500, extend life expectancy by 6 months and QALYs by 1.6 months, and reduce the cumulative incidence of heart failure by 18% at 30 years after cancer diagnosis. However, less frequent screenings are more cost-effective than the guidelines and maintain 80% of the health benefits. The ICER was most sensitive to the magnitude of ALVD treatment efficacy; higher treatment efficacy resulted in lower ICER. Lifetime non-heart failure mortality and the cumulative incidence of heart failure more than 20 years after diagnosis were extrapolated; the efficacy of ACE inhibitor and β-blocker therapy in childhood cancer survivors with ALVD is undetermined (or unknown). The COG guidelines could reduce the risk for heart failure in survivors at less than $100 000/QALY. Less frequent screening achieves most of the benefits and would be more cost-effective than the COG guidelines.

University Health Centers and Young Adult Survivors of Pediatric Cancer: Changes in Providers' Familiarity with and Practice of Survivor Care

Purpose: To describe an initiative to establish university health centers (UHC) as sites for transition to adult care for university-bound pediatric cancer survivors. UHC providers were educated about survivor care and SurvivorLink, an internet-based patient-controlled personal health record with educational resources. Changes in UHC providers' familiarity with and practice related to survivor care were measured. Methods: Lectures on survivor care were given and UHC providers were encouraged to register on SurvivorLink. During registration, providers completed a pre-survey of their familiarity with survivor care, survivor healthcare plans (SHPs), and the Children's Oncology Group Long-Term Follow-Up (COG LTFU) Guidelines, and their current practice of and comfort with providing survivor care. The follow-up survey measured the same parameters. Results were stratified based on UHC engagement: established (≥75% of UHC providers registered on SurvivorLink) and emerging (<75% registered). Results: Six universi...

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.

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.

Preferences and knowledge gaps among pediatric oncologists regarding the care of childhood cancer survivors: A survey of nearly 1,200 physicians

6561 Background: Pediatric oncologists' attitudes and knowledge about the long-term follow-up (LTFU) care of childhood cancer survivors (CCS) have not been well described. Methods: We surveyed pediatric oncologists' self-reported attitudes and knowledge regarding the LTFU care of CCS. Following a pre-notification letter, surveys with a $5 gift card were mailed to 1,173 U.S. pediatric oncologists in November 2008. A second mailing for non-responders is planned. Results: With surveys still arriving, 536 have been returned (46% response rate). Median age of respondents is 47 years (range: 32–82 years); 56% men; 69% work in a children's hospital; 17% in a cancer center; 3% in a private practice. Respondents have practiced a median 14 years (range: 1–50 years) and see a median of 23 patients/week (range: 0–250 patients/week). 70% of respondents say their center has a LTFU clinic. Choosing from closed-ended responses: 37% say they prefer to follow CCS as long as possible, 21% prefer for the patients to be followed by a physician other than themselves, and 29% are willing to follow them in the absence of a more suitable physician. In describing comfort levels in caring for CCS (1 = very uncomfortable; 7 = very comfortable), respondents were most comfortable with survivors &lt; 21 years (mean 6.2 + 1.4). For CCS &gt;21 but &lt;30 years, respondents were less comfortable (mean 5.0 + 1.5), and were uncomfortable caring for CCS &gt; 30 years (mean 3.3 + 1.7). 84% of respondents report eventually referring CCS to a LTFU program (40%), to a primary care physician (23%) or to an adult oncologist (12%). In a clinical vignette of 29 year old women exposed to mantle radiation and anthracyclines (150 mg/m2) for Hodgkin's lymphoma at 16 years of age: 30% of respondents did not appropriately recommend yearly breast cancer surveillance (based on Children's Oncology Group LTFU guidelines); 41% of respondents did not appropriately recommend cardiac surveillance; and 15% of respondents did not appropriately recommend yearly thyroid screening. Conclusions: Pediatric oncologists express a range of preferences with regard to LTFU of CCS and CCS over 21 years of age. Many appear unfamiliar with LTFU surveillance recommendations. No significant financial relationships to disclose.

Late effects on the urinary bladder in patients treated for cancer in childhood: A report from the Children's Oncology Group

Childhood cancer survivors who have had pelvic or central nervous system surgery or have received alkylator-containing chemotherapy or pelvic radiotherapy as part of their cancer therapy may experience urinary bladder late effects. This article reviews the medical literature on long-term bladder complications in survivors of childhood cancer and outlines the Children's Oncology Group Long-Term Follow-up (COG LTFU) Guidelines related to bladder function. An overview of the treatment of bladder late effects and recommended counseling for survivors with these complications are presented.

Bone Mineral Density Deficits in Survivors of Childhood Cancer: Long-term Follow-up Guidelines and Review of the Literature

The development of curative therapy for most pediatric malignancies has produced a growing population of childhood cancer survivors who are at increased risk for a variety of health problems resulting from their cancer or its treatment. Because of the fact that many treatment-related sequelae may not become clinically apparent until the survivor attains maturity or begins to age, the ability of primary care providers to anticipate late effects of treatment is essential for providing timely interventions that prevent or correct these sequelae and their adverse effects on quality of life. Altered bone metabolism during treatment for childhood cancer may interfere with attainment of peak bone mass, potentially predisposing to premature onset of and more severe complications related to osteopenia and osteoporosis. Bone mineral deficits have been reported after treatment for a variety of pediatric malignancies and represent morbidity that can be reduced or prevented through lifestyle changes and attention to other common cancer-related sequelae such as hypogonadism. The Children's Oncology Group long-term follow-up guidelines for survivors of childhood, adolescent, and young adult cancers provide risk-based surveillance recommendations that are based on expert opinion and review of the scientific literature for potential late effects of pediatric cancer therapy including osteopenia. This review summarizes the existing literature that has defined characteristics of cancer survivors at risk for bone mineral deficits and contributed to the surveillance and counseling recommendations outlined in the Children's Oncology group long-term follow-up guidelines.

Guidelines for Identification of, Advocacy for, and Intervention in Neurocognitive Problems in Survivors of Childhood Cancer

With modern therapies and supportive care, survival of childhood cancer has increased considerably. Patients who have survived cancers involving the central nervous system or who have received therapy toxic to the developing brain are at risk of long-term neurocognitive sequelae. Negative outcomes are observed most frequently in survivors of acute lymphoblastic leukemia and brain tumors. The Children's Oncology Group Long-term Follow-up Guidelines Task Force on Neurocognitive/Behavioral Complications After Childhood Cancer has generated risk-based, exposure-related guidelines designed to direct the follow-up care of survivors of pediatric malignancies based on a comprehensive literature review and expert opinion. This article expands on these guidelines by reviewing the risk factors for the development of neurocognitive sequelae and describing the expected pattern of these disabilities. We herein present recommendations for the screening and management of neurocognitive late effects and outline important areas of school and legal advocacy for survivors with disabilities. Finally, we list resources that can guide patients, their parents, and their medical caregivers as they face the long-term neurocognitive consequences of cancer therapy.

Development of Risk-Based Guidelines for Pediatric Cancer Survivors: The Children's Oncology Group Longterm Followup Guidelines From the Children's Oncology Group Late Effects Committee and Nursing Discipline

Development of Risk-Based Guidelines for Pediatric Cancer Survivors: The Children's Oncology Group Longterm Followup Guidelines From the Children's Oncology Group Late Effects Committee and Nursing Discipline

Development of Risk-Based Guidelines for Pediatric Cancer Survivors: The Children's Oncology Group Long-term Follow-up Guidelines From the Children's Oncology Group Late Effects Committee and Nursing Discipline

Development of Risk-Based Guidelines for Pediatric Cancer Survivors: The Children's Oncology Group Long-term Follow-up Guidelines From the Children's Oncology Group Late Effects Committee and Nursing Discipline