Retinopathy, Optic Neuropathy, and Cataract in Childhood Cancer Survivors Treated With Radiation Therapy: A PENTEC Comprehensive Review.

PURPOSE: Few reports describe the risks of late ocular toxicities after radiation therapy (RT) for childhood cancers despite their effect on quality of life. The Pediatric Normal Tissue Effects in the Clinic (PENTEC) ocular task force aims to quantify the radiation dose dependence of select late ocular adverse effects. Here, we report results concerning retinopathy, optic neuropathy, and cataract in childhood cancer survivors who received cranial RT. METHODS AND MATERIALS: A systematic literature search was performed using the PubMed, MEDLINE, and Cochrane Library databases for peer-reviewed studies published from 1980 to 2021 related to childhood cancer, RT, and ocular endpoints including dry eye, keratitis/corneal injury, conjunctival injury, cataract, retinopathy, and optic neuropathy. This initial search yielded abstracts for 2947 references, 269 of which were selected as potentially having useful outcomes and RT data. Data permitting, treatment and outcome data were used to generate normal tissue complication probability models. RESULTS: We identified sufficient RT data to generate normal tissue complication probability models for 3 endpoints: retinopathy, optic neuropathy, and cataract formation. Based on limited data, the model for development of retinopathy suggests 5% and 50% risk of toxicity at 42 and 62 Gy, respectively. The model for development of optic neuropathy suggests 5% and 50% risk of toxicity at 57 and 64 Gy, respectively. More extensive data were available to evaluate the risk of cataract, separated into self-reported versus ophthalmologist-diagnosed cataract. The models suggest 5% and 50% risk of self-reported cataract at 12 and >40 Gy, respectively, and 50% risk of ophthalmologist-diagnosed cataract at 9 Gy (>5% long-term risk at 0 Gy in patients treated with chemotherapy only). CONCLUSIONS: Radiation dose effects in the eye are inadequately studied in the pediatric population. Based on limited published data, this PENTEC comprehensive review establishes relationships between RT dose and subsequent risks of retinopathy, optic neuropathy, and cataract formation.

Persistent Child Poverty and Mortality in a Cohort of Children with Cancer in Alabama.

BACKGROUND: One-fifth of U.S. counties are designated persistent child poverty counties (≥20% of children in poverty since 1980). The association between a persistent child poverty environment and mortality in children with cancer is unknown. METHODS: Our cohort includes 2,089 children with cancer (2000-2016) in Alabama. We used multivariable Cox proportional hazards modeling (adjusted for sociodemographics/clinical characteristics) to assess mortality by persistent child poverty designation at 1, 5, and 10 years from diagnosis. Distance to treatment was subsequently explored. RESULTS: Forty-two percent of the cohort lived in a persistent child poverty county; they were more likely to be African American (P < 0.0001), have public/no insurance (P = 0.0009), and live >100 miles to treatment (P < 0.0001). Children in persistent child poverty counties were 30% more likely to die by 5 years [95% confidence interval (CI) = 1.06-1.59; P = 0.012]. Distance (per 20-mile increase) to treatment was associated with a 9% increased mortality risk (P < 0.0001). Children with both exposures (distance >100 miles and persistent child poverty) faced the highest mortality risk at 5 years (HR = 1.80; 95% CI = 1.39-2.33; P < 0.0001). In subanalysis, children exposed to persistent child poverty were at higher risk for cancer-related mortality. However, the risk of health-related mortality did not differ. CONCLUSIONS: Among children with cancer from the Deep South, persistent child poverty was a prevalent exposure associated with inferior overall survival. Distance to treatment was independently associated with inferior survival. Children with both exposures had the highest risk of mortality. IMPACT: Persistent child poverty is associated with inferior survival among children with cancer; mechanisms underlying this disparity warrant investigation. See related commentary by Orjuela-Grimm and Beauchemin, p. 295.

Bloom where you are planted: Hemangioma or malignancy?

Vascular anomalies comprise a spectrum of disorders characterized by the abnormal development or growth of blood and lymphatic vessels. These growths have unique features and diverse behaviors, mandating a multidisciplinary approach in their evaluation, diagnosis, and management. Here we describe the case of a male toddler presenting with an abdominal mass, originally treated as a metastatic retroperitoneal tumor, but subsequently felt to represent a vascular anomaly.

Metastatic pediatric sclerosing epithelioid fibrosarcoma.

Sclerosing epithelioid fibrosarcoma (SEF) is a rare and aggressive soft-tissue sarcoma thought to originate in fibroblasts of the tissues comprising tendons, ligaments, and muscles. Minimally responsive to conventional cytotoxic chemotherapies, >50% of SEF patients experience local recurrence and/or metastatic disease. SEF is most commonly discovered in middle-aged and elderly adults, but also rarely in children. A common gene fusion occurring between the EWSR1 and CREB3L1 genes has been observed in 80%-90% of SEF cases. We describe here the youngest SEF patient reported to date (a 3-yr-old Caucasian male) who presented with numerous bony and lung metastases. Additionally, we perform a comprehensive literature review of all SEF-related articles published since the disease was first characterized. Finally, we describe the generation of an SEF primary cell line, the first such culture to be reported. The patient described here experienced persistent disease progression despite aggressive treatment including multiple resections, radiotherapy, and numerous chemotherapies and targeted therapeutics. Untreated and locally recurrent tumor and metastatic tissue were sequenced by whole-genome, whole-exome, and deep-transcriptome next-generation sequencing with comparison to a patient-matched normal blood sample. Consistent across all sequencing analyses was the disease-defining EWSR1-CREB3L1 fusion as a single feature consensus. We provide an analysis of our genomic findings and discuss potential therapeutic strategies for SEF.

The effects of focal adhesion kinase and platelet-derived growth factor receptor beta inhibition in a patient-derived xenograft model of primary and metastatic Wilms tumor.

Aggressive therapies for patients with metastatic Wilms tumor (WT) with subsequent severe late effects warrant the search for novel therapies. The role of focal adhesion kinase (FAK), a non-receptor tyrosine kinase important in pediatric solid tumor development and progression, has not been examined in metastatic WT. Using a novel patient-derived xenograft (PDX) of a primary and matched, isogenic, metastatic WT, the hypothesis of the current study was that FAK would contribute to metastatic WT and small molecule inhibition would decrease tumor growth. Immunohistochemical staining, immunoblotting, cell viability and proliferation assays, cell cycle analysis, and cellular motility and attachment-independent growth assays were performed. FAK was present and phosphorylated in both WT PDXs and in the human samples from which they were derived. FAK inhibition decreased cellular survival, proliferation, and cell cycle progression in both PDXs but only significantly decreased migration, invasion, and attachment-independent growth in the primary WT PDX. Kinomic profiling revealed that platelet-derived growth factor receptor beta (PDGFRß) may be affected by FAK inhibition in WT. Pharmacologic inhibition of FAK and PDGFRß was synergistic in primary WT PDX cells. These findings broaden the knowledge of metastatic WT and support further investigations on the potential use of FAK and PDGFRß inhibitors.

Focal Adhesion Kinase Inhibition Contributes to Tumor Cell Survival and Motility in Neuroblastoma Patient-Derived Xenografts.

Patient-derived xenografts (PDXs) provide an opportunity to evaluate the effects of therapies in an environment that more closely resembles the human condition than that seen with long-term passage cell lines. In the current studies, we investigated the effects of FAK inhibition on two neuroblastoma PDXs in vitro. Cells were treated with two small molecule inhibitors of FAK, PF-573,228 (PF) and 1,2,4,5-benzentetraamine tetrahydrochloride (Y15). Following FAK inhibition, cell survival and proliferation decreased significantly and cell cycle arrest was seen in both cell lines. Migration and invasion assays were used to determine the effect of FAK inhibition on cell motility, which decreased significantly in both cell lines in the presence of either inhibitor. Finally, tumor cell stemness following FAK inhibition was evaluated with extreme limiting dilution assays as well as with immunoblotting and quantitative real-time PCR for the expression of stem cell markers. FAK inhibition decreased formation of tumorspheres and resulted in a corresponding decrease in established stem cell markers. FAK inhibition decreased many characteristics of the malignant phenotype, including cancer stem cell like features in neuroblastoma PDXs, making FAK a candidate for further investigation as a potential target for neuroblastoma therapy.

The presence of PIM3 increases hepatoblastoma tumorigenesis and tumor initiating cell phenotype and is associated with decreased patient survival.

PURPOSE: Hepatoblastoma is the most common primary liver cancer of childhood and has few prognostic indicators. We have previously shown that Proviral Integration site for Moloney murine leukemia virus (PIM3) kinase decreased hepatoblastoma tumorigenicity. We sought to determine the effect of PIM3 overexpression on hepatoblastoma cells and whether expression of PIM3 correlated with patient/tumor characteristics or survival. METHODS: The hepatoblastoma cell line, HuH6, and patient-derived xenograft, COA67, were utilized. Viability, proliferation, migration, sphere formation, and tumor growth in mice were assessed in PIM3-overexpressing cells. Immunohistochemistry was performed for PIM3 on patient samples. Correlation between stain score and clinical/pathologic characteristics was assessed. RESULTS: PIM3 overexpression rescued the anti-proliferative effect observed with PIM3 knockdown. Sphere formation was increased in PIM3 overexpressing cells. Cells with PIM3 overexpression yielded larger tumors than those with empty vector. Seventy-four percent of samples expressed PIM3. There was no statistical difference in patient characteristics between subjects with strong versus weak PIM3 staining, but patients with strong PIM3 staining had decreased survival. CONCLUSIONS: PIM3 expression plays a role in hepatoblastoma tumorigenesis. PIM3 was present in the majority of hepatoblastomas and higher PIM3 expression correlated with decreased survival. PIM3 warrants investigation as a therapeutic target and prognostic marker for hepatoblastoma.

A unique phenotype of T-cell acute lymphoblastic leukemia in a patient with GATA2 haploinsufficiency.

Germline or acquired mutations involving the GATA-binding protein gene (GATA2) have been linked to a variety of clinical conditions. In addition, patients harboring GATA2 mutations have a striking predisposition to develop myeloid malignancies, such as myelodysplastic syndrome or acute myeloid leukemia, but not acute lymphoblastic leukemia (ALL). We report here a unique occurrence of early T-cell precursor ALL in a young child with GATA2 haploinsufficiency.

Corruption of neuroblastoma patient derived xenografts with human T cell lymphoma.

BACKGROUND: Patient derived xenografts (PDXs) provide a unique opportunity for investigators to study tumor cell activity, response to therapeutics, and resistance patterns without exposing the human patient to experimental compounds, and thereby play a crucial role in pre-clinical evaluation of new therapies. It has been reported that PDXs may undergo a transformation to lymphoma, most commonly associated with Epstein Barr virus (EBV). If the character of a xenograft becomes compromised and remains undetected, it could have a detrimental impact on the research community as a whole. Our lab has established a number of pediatric solid tumor PDXs which accurately recapitulate the human tumors following several passages. One particular neuroblastoma PDX was noted to grow quickly and with an unusual phenotype, leading us to hypothesize that this PDX had undergone a transformation. METHODS: The PDX in question was investigated with histology, immunohistochemistry (IHC), EBER in situ hybridization, and PCR to determine its identity. RESULTS: Histology on the tumor revealed a small, round blue cell tumor similar to the original neuroblastoma from which it was derived. IHC staining showed that the tumor was composed of lymphocytes that were CD3 positive, <5% CD4 positive, and CD20 negative. The cells were Epstein Barr virus negative. PCR demonstrated that the tumor was human and not murine in origin. CONCLUSION: These findings indicate that a human T Cell lymphoma developed in place of this neuroblastoma PDX. Changes in PDX identity such as this one will significantly impact studies utilizing pediatric PDXs and the mechanism by which this occurred warrants further investigation.

Targeting PIM Kinases Affects Maintenance of CD133 Tumor Cell Population in Hepatoblastoma.

Hepatoblastoma is the most common primary liver tumor in children, but treatment has not changed significantly in the past 20 years. We have previously demonstrated that Proviral Integration site for Moloney murine leukemia (PIM) kinases promote tumorigenesis in hepatoblastoma. Stem cell-like cancer cells (SCLCCs) are a subset of cells thought to be responsible for chemoresistance, metastasis, relapse, and recurrence. The aim of this study was to identify SCLCCs in hepatoblastoma and determine the role of PIM kinases in SCLCCs. Hepatoblastoma cells were separated into CD133-enriched and CD133-depleted populations and the frequency of SCLCCs was assessed. CD133 expression was determined in the presence or absence of the PIM inhibitor, AZD1208. The effects of AZD1208 on proliferation, apoptosis, and motility were assessed in vitro and the effect of AZD1208 on tumor growth was examined in vivo. We identified CD133 as a marker for SCLCCs in hepatoblastoma and showed that PIM kinases promote a SCLCC phenotype. PIM kinase inhibition with AZD1208 decreased proliferation, migration, and invasion and increased apoptosis in both SCLCCs and non-SCLCCs in a long-term passaged hepatoblastoma cell line and patient-derived xenograft. Additionally, tumor growth in mice implanted with hepatoblastoma SCLCCs was decreased with PIM inhibition such that 57% of the tumors regressed. These findings identify CD133 as a marker for SCLCCs in hepatoblastoma and provide evidence that inhibition of PIM kinases decreases stemness and tumorigenicity of SCLCCs in hepatoblastoma, making them potential therapeutic targets for the treatment of hepatoblastoma.

Quality Initiative to Improve time to Antibiotics for Febrile Pediatric Patients with Potential Neutropenia.

INTRODUCTION: In patients who are immunocompromised, fever may indicate a life-threatening infection. Prompt time to antibiotic administration in febrile patients at risk for neutropenia has been identified by national and international panels as a key benchmark of quality care in emergent situations. A quality improvement initiative to improve health care provided in a pediatric emergency department (ED) is described. METHODS: A clinical pathway was previously initiated in a pediatric ED with a goal of improving time to antibiotics for febrile neutropenia patients. An agreed upon pathway and order set being initiated. Improvements were seen but not to the desired level. This project involved an improvement cycle that focused on nonvalue added time in the workflow. RESULTS: Percent of patients receiving antibiotics within the goal time of 1 hour increased from 40% to 80% with the intervention. Process measures including arrival to ED bed time, ED bed to antibiotic order time and antibiotic order time to delivery time were followed. CONCLUSION: Clinical guidelines, order sets and detailed understanding of the actual workflow at the point of care delivery can be instrumental in achieving the goals of reducing time to antibiotics.

Targeting PIM kinase as a therapeutic strategy in human hepatoblastoma.

Increasing incidence coupled with poor prognosis and treatments that are virtually unchanged over the past 20 years have made the need for the development of novel therapeutics for hepatoblastoma imperative. PIM kinases have been implicated as drivers of tumorigenesis in multiple cancers, including hepatocellular carcinoma. We hypothesized that PIM kinases, specifically PIM3, would play a role in hepatoblastoma tumorigenesis and that PIM kinase inhibition would affect hepatoblastoma in vitro and in vivo. Parameters including cell survival, proliferation, motility, and apoptosis were assessed in human hepatoblastoma cells following PIM3 knockdown with siRNA or treatment with the PIM inhibitor AZD1208. An in vivo model of human hepatoblastoma was utilized to study the effects of PIM inhibition alone and in combination with cisplatin. PIM kinases were found to be present in the human hepatoblastoma cell line, HuH6, and in a human hepatoblastoma patient-derived xenograft, COA67. PIM3 knockdown or inhibition with AZD1208 decreased cell survival, attachment independent growth, and motility. Additionally, inhibition of tumor growth was observed in a hepatoblastoma xenograft model in mice treated with AZD1208. Combination therapy with AZD1208 and cisplatin resulted in a significant increase in animal survival when compared to either treatment alone. The current studies showed that PIM kinase inhibition decreased human hepatoblastoma tumorigenicity both in vitro and in vivo, implying that PIM inhibitors may be useful as a novel therapeutic for children with hepatoblastoma.

Adolescent and Young Adult Oncology, Version 2.2018, NCCN Clinical Practice Guidelines in Oncology.

This selection from the NCCN Guidelines for Adolescent and Young Adult (AYA) Oncology focuses on treatment and management considerations for AYA patients with cancer. Compared with older adults with cancer, AYA patients have unique needs regarding treatment, fertility counseling, psychosocial and behavioral issues, and supportive care services. The complete version of the NCCN Guidelines for AYA Oncology addresses additional aspects of caring for AYA patients, including risk factors, screening, diagnosis, and survivorship.

Longitudinal assessment of late-onset neurologic conditions in survivors of childhood central nervous system tumors: a Childhood Cancer Survivor Study report.

Background: Survivors of childhood central nervous system (CNS) tumors experience high rates of treatment-related neurologic sequelae. Whether survivors continue to be at increased risk for new events as they age is unknown. Methods: Adverse neurologic health conditions in 5-year survivors of CNS tumors from the Childhood Cancer Survivor Study (n = 1876) were evaluated longitudinally at a median 23.0 years from diagnosis (range, 5.1-38.9), median age at last evaluation 30.3 years (range, 6.1-56.4). Multivariable regression estimated hazard ratios (HRs) and 95% CIs. Results: From 5 to 30 years post diagnosis, cumulative incidence increased for seizures from 27% to 41%, motor impairment 21% to 35%, and hearing loss 9% to 23%. Risks were elevated compared with siblings (eg, seizures HR: 12.7; 95% CI: 9.6-16.7; motor impairment HR: 7.6; 95% CI: 5.8-9.9; hearing loss HR: 18.4; 95% CI: 13.1-25.9). Regional brain doses of radiation therapy were associated with development of new deficits (eg, frontal ≥50 Gy and motor impairment HR: 2.0; 95% CI: 1.2-3.4). Increased risk for motor impairment was also associated with tumor recurrence (HR: 2.6; 95% CI: 1.8-3.8), development of a meningioma (HR: 2.3; 95% CI: 0.9-5.4), and stroke (HR: 14.9; 95% CI: 10.4-21.4). Seizure risk was doubled by recurrence (HR: 2.3; 95% CI: 1.6-3.2), meningioma (HR: 2.6; 95% CI: 1.1-6.5), and stroke (HR: 2.0; 95% CI: 1.1-3.4). Conclusions: CNS tumor survivors remain at risk for new-onset adverse neurologic events across their lifespans at a rate greater than siblings. Cranial radiation, stroke, tumor recurrence, and development of meningioma were independently associated with late-onset adverse neurologic sequelae.

CREATE Wellness: A multi-component behavioral intervention for patients not responding to traditional Cardiovascular disease management.

BACKGROUND/AIMS: Cardiovascular disease (CVD) is the leading cause of death in the US. Many patients do not benefit from traditional disease management approaches to CVD risk reduction. Here we describe the rationale, development, and implementation of a multi-component behavioral intervention targeting patients who have persistently not met goals of CVD risk factor control. METHODS: Informed by published evidence, relevant theoretical frameworks, stakeholder advice, and patient input, we developed a group-based intervention (Changing Results: Engage and Activate to Enhance Wellness; "CREATE Wellness") to address the complex needs of patients with elevated or unmeasured CVD-related risk factors. We are testing this intervention in a randomized trial among patients with persistent (i.e > 2 years) sub-optimal risk factor control despite being enrolled in an advanced and highly successful CVD disease management program. RESULTS: The CREATE Wellness intervention is designed as a 3 session, group-based intervention combining proven elements of patient activation, health system engagement skills training, shared decision making, care planning, and identification of lifestyle change barriers. Our key learnings in designing the intervention included the value of multi-level stakeholder input and the importance of pragmatic skills training to address barriers to care. CONCLUSIONS: The CREATE Wellness intervention represents an evidence-based, patient-centered approach for patients not responding to traditional disease management. The trial is currently underway at three medical facilities within Kaiser Permanente Northern California and next steps include an evaluation of efficacy, adaptation for non-English speaking patient populations, and modification of the curriculum for web- or phone-based versions. CLINICALTRIALSGOV IDENTIFIER: NCT02302612.

Demographic, medical, and psychosocial predictors of benefit finding among caregivers of childhood cancer survivors.

BACKGROUND: There is a growing body of literature examining benefit finding, or finding positive outcomes in the face of adversity, among both adults and children with chronic conditions, and to some degree among caregivers. This study examined demographic, medical, and psychosocial predictors of greater benefit finding specifically among caregivers of childhood cancer survivors. METHODS: Caregivers of children who had completed treatment for cancer (n = 83) completed measures assessing child and caregiver demographic information and caregiver coping (active, acceptance, emotion-focused, and avoidant), optimism, social support, caregiving burden, posttraumatic stress symptoms, illness impact (how much caregivers feel impacted by their child's illness in various domains), and benefit finding (positive outcomes). RESULT: Regression analyses indicated that positive spiritual coping, optimism, and illness impact uniquely predicted overall benefit finding for caregivers of childhood cancer survivors. CONCLUSION: Results point to adaptive tendencies that are associated with finding benefits when caring for a childhood cancer survivor and suggest potential avenues for intervention among this population. Copyright © 2015 John Wiley & Sons, Ltd.

Inferior outcomes for black children with high risk acute lymphoblastic leukemia and the impact of socioeconomic variables.

BACKGROUND: While significant improvements have been made for children with acute lymphoblastic leukemia (ALL) in the United States over the past 20 years, black patients continue to have inferior outcomes. The full impact of socioeconomic variables on outcomes in this minority population is not entirely understood. PROCEDURE: Disease characteristics, demographic, and socioeconomic status (SES) variables were collected on black (n = 44) and white (n = 178) patients diagnosed at the University of Alabama at Birmingham. Cox proportional hazard regression was used to evaluate the influence of SES and insurance status on survival. RESULTS: As a cohort, 5-year overall survival (OS) was 87% (82-91%), with a median follow-up of 99 months. In univariable analysis, black race was not significantly associated with a higher risk of death or relapse and death. White and black patients with standard-risk leukemia had excellent outcomes, with 97% (91-99%) and 96% (75-99%) 5-year OS, respectively. In contrast, for high-risk disease, white patients had a statistically significant improved 5-year OS rates compared with black patients (79% [68-87%] vs. 52% [28-72%]). Black children were more likely to have public insurance, and, in multivariable analysis, this was associated with a trend toward an improved outcome. Black patients also had poorer census tract-level SES parameters, but these variables were not associated with survival. CONCLUSION: Our study demonstrates significantly inferior outcomes for black children with high-risk leukemia. These outcome disparities were not related to SES variables, including poverty or private insurance coverage, suggesting the involvement of other factors and highlighting the need for a prospective investigative analysis.

Benefit Finding and Quality of Life in Caregivers of Childhood Cancer Survivors: The Moderating Roles of Demographic and Psychosocial Factors.

BACKGROUND: Benefit finding, or finding positive outcomes in the face of adversity, may play a role in predicting quality of life (QoL) among caregivers, but mixed results suggest that other factors may moderate this relationship. OBJECTIVE: This study examined demographic and psychosocial moderators of the association between benefit finding and QoL among caregivers of childhood cancer survivors. METHODS: Caregivers of childhood cancer survivors (n = 83) completed measures of benefit finding, QoL, coping, optimism, social support, caregiving demand, posttraumatic stress, and demographics. RESULTS: The relationship between benefit finding and QoL was moderated by caregiver age, marital status, socioeconomic status, geographic location, acceptance and emotion-focused coping, optimism, caregiving demand, and posttraumatic stress. Benefit finding was more strongly related to QoL among caregivers with fewer demographic/psychosocial resources. CONCLUSIONS: Results suggest that finding benefits in the cancer experience may have a greater positive impact for caregivers with relatively fewer demographic and psychosocial resources and may have less of an impact for caregivers with relatively greater resources. Findings further point to the complex nature of QoL among caregivers of childhood cancer survivors. IMPLICATIONS FOR PRACTICE: Results may aid clinicians in identifying caregivers at particular risk for low QoL. They may be counseled to find benefits in their experience or provided with resources to strengthen other factors that impact QoL.

Predictors of colorectal cancer surveillance among survivors of childhood cancer treated with radiation: a report from the Childhood Cancer Survivor Study.

BACKGROUND: Childhood cancer survivors treated with radiotherapy to a field including the colon or rectum have an elevated risk of developing radiation-induced colorectal cancer (CRC). The Children's Oncology Group recommends colonoscopy every 5 years beginning at age 35 years for at-risk survivors. METHODS: Analyses included 702 five-year survivors (Childhood Cancer Survivor Study) aged ≥36 years who received ≥30 gray of abdominal, pelvic, or spinal radiotherapy. Multivariate generalized linear models were used to calculate relative risks (RR) with 95% confidence intervals (95% CI) for adherence to the Children's Oncology Group's CRC surveillance recommendations. RESULTS: With a median age of 43 years (range, 36-58 years), 29.5% of the survivors (207 of 702 survivors) met surveillance recommendations. In multivariate analyses, age ≥50 years versus age 36 to 49 years (RR, 2.6; 95% CI, 2.0-3.4), reporting a routine cancer follow-up visit within 1 year before the study (RR, 1.5; 95% CI, 1.0-2.2), reporting ≥10 physician visits within the past year versus 0 to 9 visits (RR, 1.4; 95% CI, 1.1-1.7), and discussing future cancer risk with a physician at the time of the most recent follow-up visit (RR, 1.4; 95% CI, 1.1-1.7) were found to be associated with adherence to CRC surveillance recommendations. CONCLUSIONS: Greater than 70% of survivors at an increased risk of CRC were not screened as recommended. Regular physician contact and discussion of screening were associated with a 60% increase in CRC surveillance. Educational interventions targeted at survivors and their primary care physicians are needed to heighten knowledge of CRC risk after radiotherapy and the importance of appropriate surveillance.