Subsequent Renal Cancer Among Childhood Cancer Survivors: Analysis of Surveillance, Epidemiology, and End Results.

Renal cancer, although still rare among individuals under 45 years of age, is on the rise in the general population. The risk and timing of subsequent renal cancer in survivors of childhood cancer is not well established. Using the SEER registry, we reported the incidence of subsequent malignant renal neoplasms after treatment for primary malignancy diagnosed under 20 years of age. We evaluated clinical characteristics, standardized incidence ratio (SIR), and Kaplan-Meier survival estimates. Fifty-three survivors developed subsequent renal cancer (54 total cases). Of these, 54.7% were female, 88.7% were white, and 13.2% were Hispanic. Mean ages at primary malignancy and subsequent renal cancer were 10.1 and 31.1 years, respectively. Forty-seven cases were second cancers, 6 were third, and 1 was fourth. For survivors of childhood cancer, the overall SIR for renal cancer was 4.52 (95% CI: 3.39-5.89). The 5-year overall survival rate after development of subsequent renal cancer was 73% (95% CI: 58%-83%). Renal cancer occurs 4.5 times more frequently in childhood cancer survivors than in the general population, necessitating long-term care considerations.

Adolescent and Young Adult (AYA) Oncology, Version 2.2024, NCCN Clinical Practice Guidelines in Oncology.

This selection from the NCCN Guidelines for Adolescent and Young Adult (AYA) Oncology focuses on considerations for the comprehensive care of 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 Adolescent and Young Adult (AYA) Oncology addresses additional aspects of caring for AYA patients, including risk factors, screening, diagnosis, and survivorship.

What Are Risk Factors for and Outcomes of Late Amputation After Treatment for Lower Extremity Sarcoma: A Childhood Cancer Survivor Study Report.

BACKGROUND: Although pediatric lower extremity sarcoma once was routinely treated with amputation, multiagent chemotherapy as well as the evolution of tumor resection and reconstruction techniques have enabled the wide adoption of limb salvage surgery (LSS). Even though infection and tumor recurrence are established risk factors for early amputation (< 5 years) after LSS, the frequency of and factors associated with late amputation (≥ 5 years from diagnosis) in children with sarcomas are not known. Additionally, the resulting psychosocial and physical outcomes of these patients compared with those treated with primary amputation or LSS that was not complicated by subsequent amputation are not well studied. Studying these outcomes is critical to enhancing the quality of life of patients with sarcomas. QUESTIONS/PURPOSES: (1) How have treatments changed over time in patients with lower extremity sarcoma who are included in the Childhood Cancer Survivor Study (CCSS), and did primary treatment with amputation or LSS affect overall survival at 25 years among patients who had survived at least 5 years from diagnosis? (2) What is the cumulative incidence of amputation after LSS for patients diagnosed with pediatric lower extremity sarcomas 25 years after diagnosis? (3) What are the factors associated with time to late amputation (≥ 5 years after diagnosis) in patients initially treated with LSS for lower extremity sarcomas in the CCSS? (4) What are the comparative social, physical, and emotional health-related quality of life (HRQOL) outcomes among patients with sarcoma treated with primary amputation, LSS without amputation, or LSS complicated by late amputation, as assessed by CCSS follow-up questionnaires, the SF-36, and the Brief Symptom Inventory-18 at 20 years after cancer diagnosis? METHODS: The CCSS is a long-term follow-up study that began in 1994 and is coordinated through St. Jude Children's Research Hospital. It is a retrospective study with longitudinal follow-up of more than 38,000 participants treated for childhood cancer when younger than 21 years at one of 31 collaborating institutions between 1970 and 1999 in the United States and Canada. Participants were eligible for enrollment in the CCSS after they had survived 5 years from diagnosis. Within the CCSS cohort, we included participants who had a diagnosis of lower extremity sarcoma treated with primary amputation (547 patients with a mean age at diagnosis of 13 ± 4 years) or primary LSS (510 patients with a mean age 14 ± 4 years). The LSS cohort was subdivided into LSS without amputation, defined as primary LSS without amputation at the time of latest follow-up; LSS with early amputation, defined as LSS complicated by amputation occurring less than 5 years from diagnosis; or LSS with late amputation, defined as primary LSS in study patients who subsequently underwent amputation 5 years or more from cancer diagnosis. The cumulative incidence of late amputation after primary LSS was estimated. Cox proportional hazards regression with time-varying covariates identified factors associated with late amputation. Modified Poisson regression models were used to compare psychosocial, physical, and HRQOL outcomes among patients treated with primary amputation, LSS without amputation, or LSS complicated by late amputation using validated surveys. RESULTS: More study participants were treated with LSS than with primary amputation in more recent decades. The overall survival at 25 years in this population who survived 5 years from diagnosis was not different between those treated with primary amputation (87% [95% confidence interval [CI] 82% to 91%]) compared with LSS (88% [95% CI 85% to 91%]; p = 0.31). The cumulative incidence of amputation at 25 years after cancer diagnosis and primary LSS was 18% (95% CI 14% to 21%). With the numbers available, the cumulative incidence of late amputation was not different among study patients treated in the 1970s (27% [95% CI 15% to 38%]) versus the 1980s and 1990s (19% [95% CI 13% to 25%] and 15% [95% CI 10% to 19%], respectively; p = 0.15). After controlling for gender, medical and surgical treatment variables, cancer recurrence, and chronic health conditions, gender (hazard ratio [HR] 2.02 [95% CI 1.07 to 3.82]; p = 0.03) and history of prosthetic joint reconstruction (HR 2.58 [95% CI 1.37 to 4.84]; p = 0.003) were associated with an increased likelihood of late amputation. Study patients treated with a primary amputation (relative risk [RR] 2.04 [95% CI 1.15 to 3.64]) and LSS complicated by late amputation (relative risk [RR] 3.85 [95% CI 1.66 to 8.92]) were more likely to be unemployed or unable to attend school than patients treated with LSS without amputation to date. The CCSS cohort treated with primary amputation and those with LSS complicated by late amputation reported worse physical health scores than those without amputation to date, although mental and emotional health outcomes did not differ between the groups. CONCLUSION: There is a substantial risk of late amputation after LSS, and both primary and late amputation status are associated with decreased physical HRQOL outcomes. Children treated for sarcoma who survive into adulthood after primary amputation and those who undergo late amputation after LSS may benefit from interventions focused on improving physical function and reaching educational and employment milestones. Efforts to improve the physical function of people who have undergone amputation either through prosthetic design or integration into the residuum should be supported. Understanding factors associated with late amputation in the setting of more modern surgical approaches and implants will help surgeons more effectively manage patient expectations and adjust practice to mitigate these risks over the life of the patient. LEVEL OF EVIDENCE: Level III, therapeutic study.

A portable survivorship care plan: a tool that helps educate and improve knowledge in childhood cancer survivors.

PURPOSE: There is a growing population of survivors of childhood cancer at risk for late effects that can affect their overall quality of life. There is evidence that they have inadequate knowledge about their diagnosis, treatment, and subsequent late effects. A randomized study was conducted to determine if a portable credit card-sized plastic card, the "Survivor Healthcare Passport," improved the survivor's knowledge of diagnosis, treatment, risks, and follow-up care. The study included 126 patients 2 years post-end of cancer treatment and took place at the UCSF Benioff Children's Hospital Survivorship Clinic. METHODS: Patients attending the UCSF Survivorship clinic were randomized to receive or not receive a passport at their first survivorship clinic visit. Each groups' knowledge of diagnosis, treatment history, and follow-up needs was assessed at three time points with a questionnaire. RESULTS: Patients who received the passport distributed immediately after their visit demonstrated improved and sustained knowledge compared with survivors who did not receive the passport until more than 4 months later. CONCLUSION: Enhancing a survivor's knowledge is an important endeavor and a continual challenge for practitioners in survivorship clinics. This portable educational tool helps improve patient knowledge of their cancer, therapy, and follow-up needs. By providing a tangible card that is quick and easy to access, survivors have access to their treatment late effects and follow-up needs that can also be shared with other healthcare providers.

Frequency of face touching with and without a mask in pediatric hematology/oncology health care professionals.

The impact of wearing a mask on face-touching behavior is unknown. We conducted a survey of pediatric hematology/oncology staff to assess the perception of how masks would affect face-touching behavior and a brief observational study of providers during conferences in a children's hospital to quantify how masks affect face-touching behavior. Most felt that the mask would either increase (37.4%) or decrease (36.6%) their face-touching behavior. During a total of 330 person-minutes of observation, median face-touching rate was 5.4 face touches/hour (FT/h) while wearing a mask and 20 FT/h without a mask. Masks may reduce face-touching behavior amongst health care professionals.

Germline MUTYH Mutation in a Pediatric Cancer Survivor Developing a Secondary Malignancy.

Radiotherapy-induced second malignant neoplasms (SMNs) are a severe late complication in pediatric cancer survivors. Germline mutations in tumor suppressor genes contribute to SMNs; however, the most relevant germline variants mediating susceptibility are not fully defined. The authors performed matched whole-exome sequencing analyses of germline and tumor DNA from 4 pediatric solid tumor survivors who subsequently developed radiation-associated SMNs. Pathogenic and predicted deleterious germline variants were identified for each patient and validated with Sanger sequencing. These germline variants were compared with germline variants in a cohort of 59 pediatric patients diagnosed with primary sarcomas. Pathway analysis was performed to test for similarities in the germline variant profiles between individuals diagnosed with SMNs or primary sarcomas. One index patient was found to have a pathogenic germline monoallelic mutation in the MUTYH gene, which encodes the base excision repair enzyme adenine DNA glycosylase. This specific germline mutation is associated with a form of familial adenomatous polyposis, a new diagnosis in the patient. Germline-level genetic similarity exists between SMN-developing patients and patients developing primary sarcomas, with relevant genes involved in signal transduction and DNA repair mechanisms. The authors identify a germline MUTYH mutation in a pediatric cancer survivor developing an SMN. Germline mutations involving specific pathways such as base excision repair may identify individuals at risk for developing SMNs. The composition of germline variants in individual patients may enable estimates of patient-specific risk for developing SMNs. The authors anticipate that further analyses of germline genomes and epigenomes will reveal diverse genes and mechanisms influencing cancer risk.

A phase II study of eribulin in recurrent or refractory osteosarcoma: A report from the Children's Oncology Group.

BACKGROUND: Patients with recurrent or refractory osteosarcoma have a poor prognosis with less than 30% surviving two years. Eribulin is a synthetic analog of halichondrin B, has a novel mechanism of action when compared with other microtubule inhibitors, and may have antitumor activity in osteosarcoma. METHODS: A prospective study was designed to assess the disease control success at four months and objective response rates in patients with recurrent or refractory osteosarcoma treated with eribulin. Eligible patients were between 12 and 50 years of age, had measurable tumor, and met standard organ function requirements. Patients were given eribulin 1.4 mg/m2 /dose on days 1 and 8 of each 3-week cycle for up to 24 months if there was no progressive disease. Response to therapy was assessed using RECIST 1.1 criteria after cycles 2 and 5 and every fourth cycle thereafter. RESULTS: Nineteen patients enrolled on the AOST1322 study. The median age of enrollment was 16 years (range, 12-25 years). Twelve patients were male and seven female. Eribulin was well tolerated, with neutropenia identified as the most common toxicity. The median progression-free survival was 38 days and no patients reached the four-month time point without progression. No objective responses were seen in any patient. CONCLUSION: This study rapidly assessed the clinical activity of a novel agent in this patient population. Eribulin was well tolerated, but there were no patients who demonstrated objective response, and all patients had progression prior to four months.

Long-term sequelae in survivors of childhood leukemia with Down syndrome: A childhood cancer survivor study report.

BACKGROUND: Children with Down syndrome (DS) are at increased risk of developing acute leukemia and are more prone to acute toxicities. We studied the incidence and severity of chronic health conditions among survivors of childhood leukemia with DS compared with those without DS. METHODS: Chronic health conditions reported by questionnaire were compared between 154 pediatric leukemia survivors with DS and 581 without DS, matched by leukemia, age at diagnosis, race/ethnicity, sex, radiation location and chemotherapy exposure using Cox models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Subjects were selected from 7139 5-year survivors of leukemia in the Childhood Cancer Survivor Study. RESULTS: Risk of at least 1 late onset chronic health condition (grade 1-5) was similar in the DS population compared with the non-DS group (HR, 1.1; 95% CI, 0.7-1.5). Serious chronic health conditions (grade 3-5) were more common in DS survivors (HR, 1.7; 95% CI, 1.1-2.6), as were ≥ 3 chronic health conditions (grades 1-5) (HR, 1.7; 95% CI, 1.2-2.4). The 25-year cumulative incidence of any condition (grades 1-5) was 83% for DS survivors and 69% for non-DS survivors. CONCLUSION: Leukemia survivors with DS have therapy-related chronic health conditions comparable to those of similarly treated survivors without DS, with a few notable exceptions: 1) an increased risk of cataracts, hearing loss, and thyroid dysfunction compared with survivors without DS (though these are known risks in the DS population), 2) decreased risk of second cancers, and 3) increased risk of severe or multiple conditions. Practitioners should be aware of these risks during and after therapy. Cancer 2018;124:617-25. © 2017 American Cancer Society.

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.

Comparison of MAPIE versus MAP in patients with a poor response to preoperative chemotherapy for newly diagnosed high-grade osteosarcoma (EURAMOS-1): an open-label, international, randomised controlled trial.

BACKGROUND: We designed the EURAMOS-1 trial to investigate whether intensified postoperative chemotherapy for patients whose tumour showed a poor response to preoperative chemotherapy (≥10% viable tumour) improved event-free survival in patients with high-grade osteosarcoma. METHODS: EURAMOS-1 was an open-label, international, phase 3 randomised, controlled trial. Consenting patients with newly diagnosed, resectable, high-grade osteosarcoma aged 40 years or younger were eligible for randomisation. Patients were randomly assigned (1:1) to receive either postoperative cisplatin, doxorubicin, and methotrexate (MAP) or MAP plus ifosfamide and etoposide (MAPIE) using concealed permuted blocks with three stratification factors: trial group; location of tumour (proximal femur or proximal humerus vs other limb vs axial skeleton); and presence of metastases (no vs yes or possible). The MAP regimen consisted of cisplatin 120 mg/m2, doxorubicin 37·5 mg/m2 per day on days 1 and 2 (on weeks 1 and 6) followed 3 weeks later by high-dose methotrexate 12 g/m2 over 4 h. The MAPIE regimen consisted of MAP as a base regimen, with the addition of high-dose ifosfamide (14 g/m2) at 2·8 g/m2 per day with equidose mesna uroprotection, followed by etoposide 100 mg/m2 per day over 1 h on days 1-5. The primary outcome measure was event-free survival measured in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT00134030. FINDINGS: Between April 14, 2005, and June 30, 2011, 2260 patients were registered from 325 sites in 17 countries. 618 patients with poor response were randomly assigned; 310 to receive MAP and 308 to receive MAPIE. Median follow-up was 62·1 months (IQR 46·6-76·6); 62·3 months (IQR 46·9-77·1) for the MAP group and 61·1 months (IQR 46·5-75·3) for the MAPIE group. 307 event-free survival events were reported (153 in the MAP group vs 154 in the MAPIE group). 193 deaths were reported (101 in the MAP group vs 92 in the MAPIE group). Event-free survival did not differ between treatment groups (hazard ratio [HR] 0·98 [95% CI 0·78-1·23]); hazards were non-proportional (p=0·0003). The most common grade 3-4 adverse events were neutropenia (268 [89%] patients in MAP vs 268 [90%] in MAPIE), thrombocytopenia (231 [78% in MAP vs 248 [83%] in MAPIE), and febrile neutropenia without documented infection (149 [50%] in MAP vs 217 [73%] in MAPIE). MAPIE was associated with more frequent grade 4 non-haematological toxicity than MAP (35 [12%] of 301 in the MAP group vs 71 [24%] of 298 in the MAPIE group). Two patients died during postoperative therapy, one from infection (although their absolute neutrophil count was normal), which was definitely related to their MAP treatment (specifically doxorubicin and cisplatin), and one from left ventricular systolic dysfunction, which was probably related to MAPIE treatment (specifically doxorubicin). One suspected unexpected serious adverse reaction was reported in the MAP group: bone marrow infarction due to methotrexate. INTERPRETATION: EURAMOS-1 results do not support the addition of ifosfamide and etoposide to postoperative chemotherapy in patients with poorly responding osteosarcoma because its administration was associated with increased toxicity without improving event-free survival. The results define standard of care for this population. New strategies are required to improve outcomes in this setting. FUNDING: UK Medical Research Council, National Cancer Institute, European Science Foundation, St Anna Kinderkrebsforschung, Fonds National de la Recherche Scientifique, Fonds voor Wetenschappelijk Onderzoek-Vlaanderen, Parents Organization, Danish Medical Research Council, Academy of Finland, Deutsche Forschungsgemeinschaft, Deutsche Krebshilfe, Federal Ministry of Education and Research, Semmelweis Foundation, ZonMw (Council for Medical Research), Research Council of Norway, Scandinavian Sarcoma Group, Swiss Paediatric Oncology Group, Cancer Research UK, National Institute for Health Research, University College London Hospitals, and Biomedical Research Centre.

Increased risk of second malignant neoplasms in adolescents and young adults with cancer.

BACKGROUND: The authors describe the incidence and characteristics of secondary malignant neoplasms (SMNs) in adolescent and young adult (AYA) cancer survivors compared with those in younger and older cancer survivors. METHODS: Children aged ≤ 14 years, AYAs aged 15 to 39, and older adults aged ≥ 40 years at the time of primary diagnosis who were reported as cancer survivors in the Surveillance, Epidemiology, and End Results (SEER) program between 1973 and 2011 were compared in this population-based analysis. The primary analysis was the risk that an SMN would occur ≥ 5 years after the original diagnosis for patients who had the more common AYA cancers (leukemia, lymphoma, testicular malignancy, ovarian malignancy, melanoma, and cancers of the thyroid, breast, soft tissue, or bone). The standardized incidence ratio (SIR), absolute excess risk (AER), and cumulative incidence of SMN for the selected cancers were assessed. The risk of SMN for the entire cohort also was analyzed. RESULTS: Of the 148,558 AYA survivors who were diagnosed with a selected cancer, 7384 developed an SMN 5 years after their original diagnosis. The SIRs (95% confidence intervals [CIs]) were 1.58 (95% CI, 1.55-1.62) for AYAs, 4.26 (95% CI, 3.77-4.80) for children, and 1.10 (95% CI, 1.09-1.11) for older adults, and the AERs were 22.9, 16.6, and 14.7, respectively. The cumulative incidence of SMN at 30 years was 13.9% for the AYA group. The most common SMNs in AYAs were breast cancer, gastrointestinal cancer, genital cancers, and melanoma. AYAs who had received radiation therapy had a higher cumulative incidence of SMN. CONCLUSIONS: AYAs who survive cancer for more than 5 years have a higher relative risk of SMN compared with the general population and have a higher absolute risk of SMN compared with younger or older cancer survivors.

Conditional Survival and Predictors of Late Death in Patients With Ewing Sarcoma.

PURPOSE: Long-term survivors of Ewing sarcoma (EWS) are at considerable risk for future complications, including late relapse and death. Data on prognostic factors for late death in those who have survived beyond 5 years are lacking. METHODS: We conducted a retrospective cohort study using the Surveillance, Epidemiology, and End Results database. We obtained clinical features and outcome data on 1,351 patients with EWS who had survived 60 months or more. From these data, we performed univariate and multivariable analyses of overall survival (OS) using log-rank tests and Cox proportional hazard models. RESULTS: Of 1,351 patients in the cohort, there were 209 deaths, 144 (69%) of which were reported to be due to EWS. The OS for 5-year survivors at 10 years was 87.5% (95% confidence interval 85.4-89.3%). Univariate adverse prognostic factors for late death in 5-year survivors included age ≥ 18 years at initial diagnosis, male sex, and axial/pelvic primary site. Initial stage was not prognostic. Independent adverse prognostic factors for late death included black race (hazard ratio [HR] 2.16, P = 0.01), age ≥ 18 years at diagnosis (HR 2.02, P < 0.001), male sex (HR 1.43, P = 0.01), and axial/pelvic primary site (HR 1.43, P = 0.02). CONCLUSIONS: The majority of late deaths in 5-year survivors are due to EWS. Black race, age ≥18 at diagnosis, male sex, and axial/pelvic primary site (but not stage at diagnosis) are independently associated with increased risk of late death.

Clinical features and outcomes of infants with Ewing sarcoma under 12 months of age.

BACKGROUND: Ewing sarcoma peaks in incidence in adolescence. Infants <12 months old have rarely been reported. We aimed to compare clinical features, treatment, and survival of infants <12 months to those of older pediatric patients with Ewing sarcoma. PROCEDURE: We utilized the SEER database to identify patients <12 months of age diagnosed with Ewing sarcoma between 1973 and 2011. We used Fisher exact tests to compare clinical features and treatment modalities between these patients and patients aged 1-19 years. We used Kaplan-Meier methods to describe overall survival in these two groups. RESULTS: Of 1,957 patients in the cohort, 39 (2.0%) were diagnosed at <12 months of age. Infants had a different distribution of primary tumor sites, with lower extremity tumors under represented. Compared to older patients, infants were more likely to have soft tissue tumors (81.6% vs. 27.1%; P < 0.001); have primitive neuroectodermal tumor/Askin tumor (61.5% vs. 19.9%; P < 0.001); and have tumors <8 cm (81.0% vs. 53.2%; P < 0.014). Infants were less likely to receive radiation therapy (13.2% vs. 53.3%; P < 0.001). Infants were at increased risk for early death (P < 0.013 by Wilcoxon), though long-term overall survival was not different between age groups (P < 0.25 by log rank). CONCLUSIONS: Ewing sarcoma is rare in infants, with different clinical presentations and treatment approaches. These patients appear to be at higher risk for early death, but long-term survival is similar to older pediatric patients.

Second malignant neoplasms among children, adolescents and young adults with Wilms tumor.

BACKGROUND: The goal of this study was to describe the incidence, characteristics, and outcomes of secondary malignant neoplasms (SMN) in survivors of Wilms tumor. PROCEDURES: Patients who were 0-20 years of age at time of primary diagnosis with Wilms tumor and reported to the Surveillance, Epidemiology, and End Results [SEER] program between 1973 and 2011 were eligible for inclusion in the cohort. We used competing risks methods to estimate the cumulative incidence of SMNs and assess contributing factors for developing SMN. We estimated standardized incidence ratios (SIR), absolute excess risk and overall survival after SMN using standard methods. RESULTS: Within the SEER database, 2,851 patients were diagnosed with Wilms tumor as their first malignancy. Of these, 34 patients were reported to have a SMN. Cumulative incidence of for a secondary malignancy was 0.6% (95% confidence interval [95% CI] 0.3-1.0%) at 10 years, 1.6% (95% CI 1.0-2.3%) at 20 years, and 3.8% (95% CI 2.4-5.9%) at 30 years. Median time from primary diagnosis to SMN diagnosis was 12.5 years. SIR for SMN for survivors of Wilms tumor was 3.4 (95% CI 2.2-4.9) with an absolute excess risk of 7.6 per 10,000 persons per year. Exposure to radiation did not significantly increase risk for development of second malignancy. Overall survival for patients with SMN was 64.5% at 5 years. CONCLUSION: Survivors of Wilms tumor are at an increased risk of SMN compared to the general population, but the added risk is relatively small compared to other pediatric cancers.

Secondary malignant neoplasms among children, adolescents, and young adults with osteosarcoma.

BACKGROUND: As patients with osteosarcoma become long-term survivors, increasing attention has turned to the burden of late effects. The goal of the current study was to describe the incidence, characteristics, and outcomes of secondary malignant neoplasms (SMNs) in this population. METHODS: Patients aged birth to 40 years at time of primary diagnosis with osteosarcoma and reported to the Surveillance, Epidemiology, and End Results (SEER) program between 1973 and 2010 were eligible for inclusion in the cohort. Competing risks methods were used to estimate the cumulative incidence of SMNs and potential risk factors for developing an SMN. Standardized incidence ratios (SIR) and overall survival after an SMN were estimated. RESULTS: The SEER database included 3379 patients who were diagnosed with osteosarcoma as their first malignancy. Of these, 89 patients were diagnosed with an SMN. The cumulative incidence of any SMN was 2.1% (95% confidence interval [95% CI], 1.6%-2.7%) at 10 years, 4.0% (95% CI, 3.1%-5.1%) at 20 years, and 7.4% (95% CI, 5.6%-9.5%) at 30 years. The median time from the primary diagnosis to an SMN diagnosis was 6.0 years. The SIR for SMNs for survivors of osteosarcoma compared with the general population was 1.6 (95% CI, 1.0-2.5) for patients diagnosed with osteosarcoma from 1973 through 1985 and 4.7 (95% CI, 3.3-6.4) for patients diagnosed with osteosarcoma from 1986 through 2010, with a 34-fold increased risk of leukemia in this most recent era. The overall survival rate at 5 years for patients with SMNs after a diagnosis of osteosarcoma was 44.5%. CONCLUSIONS: Survivors of osteosarcoma are at an increased risk of developing SMNs compared with the baseline population, with an increased risk noted in patients treated in the more recent era.

Adolescent and young adult oncology, version 2.2014.

The NCCN Guidelines Insights on Adolescent and Young Adult (AYA) Oncology discuss the fertility and endocrine issues that are relevant to the management of AYA patients with cancer. Fertility preservation should be an essential part in the treatment of AYA patients with cancer. The NCCN Guidelines recommend discussion of fertility preservation and contraception before the start of treatment. Oophoropexy and embryo cryopreservation are the 2 established options for fertility preservation in women. Semen cryopreservation before the start of treatment is the most reliable and well-established method of preserving fertility in men. AYA women with cancer also have unique contraception needs, depending on the type of cancer, its treatment, and treatment-related complications. Management of cancer during pregnancy poses significant diagnostic and therapeutic challenges for both the patient and the physician. AYA women diagnosed with cancer during pregnancy require individualized treatment from a multidisciplinary team involving medical, surgical, radiation, and gynecologic oncologists; obstetricians; and perinatologists.

Comparison of Latino and non-Latino patients with Ewing sarcoma.

BACKGROUND: Ewing sarcoma (ES) is a malignancy of bone and soft tissue in children and adults. Previous registry-based studies indicate that Latino patients with ES have inferior outcomes compared to non-Latino patients, though an etiology for this difference could not be identified. To explore possible differences that might underlie this disparity, we conducted a retrospective study to compare clinical characteristics, tumor features, healthcare access, and treatment outcomes between Latino and non-Latino patients with ES. METHODS: Primary data for 218 ES patients treated at two academic medical centers between 1980 and 2010 were collected. Categorical data were compared using Fisher exact tests; Wilcoxon rank-sum tests were used for continuous variables. Survival was estimated using Kaplan-Meier analysis and compared using log-rank testing. RESULTS: Latino patients were diagnosed at a younger age (P = 0.014). All other clinical and histological data were similar between groups, including radiologic and histologic response to neoadjuvant chemotherapy. Latino patients had lower socioeconomic status (P = 0.001), were less likely to have insurance (P = 0.001), and were more likely to present to the emergency room at onset of symptoms (P = 0.031) rather than to primary care physicians. Five-year event free survival (EFS) and overall survival (OS) were similar between Latino and non-Latino patients (EFS: 60.5% vs. 50.9% P = 0.37; OS: 77.6% vs. 68.6% P = 0.54). CONCLUSION: Latino patients with ES present at a younger age, and have evidence of impaired access to healthcare. Response to initial therapy appears similar between Latino and non-Latino patients.

Pulmonary coccidiomycosis masquerading as refractory metastatic Ewing sarcoma.

We report the case of a patient who presented with a large pelvic mass, which was biopsy-proven to be Ewing sarcoma. The patient was also found to have 18 pulmonary lesions on a staging CT that were presumed to represent metastatic disease. After induction chemotherapy, a PET/CT scan revealed a marked reduction in his pelvic mass along with improvement in nearly all his pulmonary lesions except 2, which increased in size. The mixed response to chemotherapy was unusual and the decision was made to resect one of the growing lesions. Fungal culture from the excised lesion grew Coccidioides immitis.

Clinical features and outcomes in patients with secondary Ewing sarcoma.

BACKGROUND: Ewing sarcoma (EWS) is rarely diagnosed as a second malignancy. We sought to describe a cohort of patients with secondary EWS and investigate if patient characteristics and survival differ between patients with secondary and primary EWS. PROCEDURE: Patients with EWS or peripheral primitive neuroectodermal tumor (PNET) reported to the Surveillance, Epidemiology, and End Results Program (SEER) database from 1973 to 2008 were evaluated based on primary or secondary tumor sequence. Overall survival was estimated by Kaplan-Meier methods and evaluated using the log-rank test. Competing risk analysis was used to describe risk of death due to malignancy rather than other causes. RESULTS: Fifty-eight cases of secondary EWS were reported, accounting for 2.1% of all EWS cases. The median latency from primary malignancy to secondary EWS was 64 months (range 1-282 months). 12.1% of patients with secondary EWS received radiation to the site of secondary tumor during therapy for their primary malignancy. Patients with secondary EWS were more likely to have axial tumors (77.4% vs. 62.5%; P = 0.03) and smaller tumors (75.0% vs. 48.2% <8 cm; P = 0.001). Five-year overall survival from diagnosis was inferior for patients with secondary compared to primary EWS (34.3% vs. 52.2%; P = 0.002). However, patients with secondary tumors were less likely than those with primary EWS to die from their malignancy [hazard ratio 0.44; 95% confidence interval (CI) 0.23-0.85]. CONCLUSIONS: Secondary EWS accounts for a minority of cases of EWS. Tumor size and site and patient survival differ among patients with primary and secondary EWS.

Survivors of childhood cancer have increased risk of gastrointestinal complications later in life.

BACKGROUND & AIMS: Children who receive cancer therapy experience numerous acute gastrointestinal (GI) toxicities. However, the long-term GI consequences have not been extensively studied. We evaluated the incidence of long-term GI outcomes and identified treatment-related risk factors. METHODS: Upper GI, hepatic, and lower GI adverse outcomes were assessed in cases from participants in the Childhood Cancer Survivor Study, a study of 14,358 survivors of childhood cancer who were diagnosed between 1970 and 1986; data were compared with those from randomly selected siblings. The median age at cancer diagnosis was 6.8 years (range, 0-21.0 years), and the median age at outcome assessment was 23.2 years (5.6-48.9 years) for survivors and 26.6 years (1.8-56.2 years) for siblings. Rates of self-reported late GI complications (occurred 5 or more years after cancer diagnosis) were determined and associated with patient characteristics and cancer treatments, adjusting for age, sex, and race. RESULTS: Compared with siblings, survivors had increased risk of late-onset complications of the upper GI tract (rate ratio [RR], 1.8; 95% confidence interval [CI], 1.6-2.0), liver (RR, 2.1; 95% CI, 1.8-2.5), and lower GI tract (RR, 1.9; 95% CI, 1.7-2.2). The RRs for requiring colostomy/ileostomy, liver biopsy, or developing cirrhosis were 5.6 (95% CI, 2.4-13.1), 24.1 (95% CI, 7.5-77.8), and 8.9 (95% CI, 2.0-40.0), respectively. Older age at diagnosis, intensified therapy, abdominal radiation, and abdominal surgery increased the risk of certain GI complications. CONCLUSIONS: Individuals who received therapy for cancer during childhood have an increased risk of developing GI complications later in life.