Fertility preservation in children and young adults with cancer.

PURPOSE OF REVIEW: The issue of fertility preservation has become increasingly relevant as survival rates of children with cancer exceeds 80% at 5 years. Fertility preservation options are being utilized alongside less gonadotoxic therapeutic regimens in the treatment of these patients. The purpose of this review is to summarize the recent advances in fertility preservation in the pediatric, adolescent, and young adult population. RECENT FINDINGS: Education research involves both patient and provider; to increase understanding on both sides for improved adoption of techniques and higher rates of posttreatment fertility. Basic science research, specific to the pediatric population, has worked to further understanding of protective techniques and cryopreserved tissue transfer. Research on the techniques of preservation confirms the safety of surgical gonadal (ovarian and testicular) tissue retrieval for cryopreservation but a viable pathway for testicular tissue utilization, as it has for ovarian, has yet to be realized. Outcomes may be improving but it is apparent that robust registries are necessary to track patients long-term. Possibly the largest advancement in the recent past are group efforts, such as by PanCareLIFE, to create guidelines for these issues using larger cohorts and registries than were available. SUMMARY: Current research implies the need for the development of a national strategy to ensure that pediatric patients undergoing gonadotoxic regimens are educated, alongside their family, about fertility options and outcomes thereafter.

Fertility preservation for female patients with childhood, adolescent, and young adult cancer: recommendations from the PanCareLIFE Consortium and the International Late Effects of Childhood Cancer Guideline Harmonization Group.

Female patients with childhood, adolescent, and young adult cancer are at increased risk for fertility impairment when treatment adversely affects the function of reproductive organs. Patients and their families desire biological children but substantial variations in clinical practice guidelines reduce consistent and timely implementation of effective interventions for fertility preservation across institutions. As part of the PanCareLIFE Consortium, and in collaboration with the International Late Effects of Childhood Cancer Guideline Harmonization Group, we reviewed the current literature and developed a clinical practice guideline for fertility preservation in female patients who were diagnosed with childhood, adolescent, and young adult cancer at age 25 years or younger, including guidance on risk assessment and available methods for fertility preservation. The Grading of Recommendations Assessment, Development and Evaluation methodology was used to grade the available evidence and to form the recommendations. This clinical practice guideline leverages existing evidence and international expertise to develop transparent recommendations that are easy to use to facilitate the care of female patients with childhood, adolescent, and young adult cancer who are at high risk for fertility impairment. A complete review of the existing evidence, including a quality assessment, transparent reporting of the guideline panel's decisions, and achievement of global interdisciplinary consensus, is an important result of this intensive collaboration.

Communication and ethical considerations for fertility preservation for patients with childhood, adolescent, and young adult cancer: recommendations from the PanCareLIFE Consortium and the International Late Effects of Childhood Cancer Guideline Harmonization Group.

Patients with childhood, adolescent, and young adult cancer who will be treated with gonadotoxic therapies are at increased risk for infertility. Many patients and their families desire biological children but effective communication about treatment-related infertility risk and procedures for fertility preservation does not always happen. The PanCareLIFE Consortium and the International Late Effects of Childhood Cancer Guideline Harmonization Group reviewed the literature and developed a clinical practice guideline that provides recommendations for ongoing communication methods for fertility preservation for patients who were diagnosed with childhood, adolescent, and young adult cancer at age 25 years or younger and their families. Moreover, the guideline panel formulated considerations of the ethical implications that are associated with these procedures. Grading of Recommendations Assessment, Development and Evaluation methodology was used to grade the evidence and recommendations. In this clinical practice guideline, existing evidence and international expertise are combined to develop transparent recommendations that are easy to use to facilitate ongoing communication between health-care providers and patients with childhood, adolescent, and young adult cancer who might be at high risk for fertility impairment and their families.

Treatment of posttransplant lymphoproliferative disorder with poor prognostic features in children and young adults: Short-course EPOCH regimens are safe and effective.

No guidelines exist for which intensive chemotherapy regimen is best in pediatric or young adult patients with high-risk posttransplant lymphoproliferative disorder (PTLD). We retrospectively reviewed patients with PTLD who received interval-compressed short-course etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin (SC-EPOCH) regimens at our institution. Eight patients were included with median age of 12 years. All patients achieved a complete response with a manageable toxicity profile. Two patients developed second, clonally unrelated, EBV-positive PTLD and one patient had recurrence at 6 months off therapy. No graft rejection occurred during therapy. All eight patients are alive with median follow-up of 29 months.

Hypothalamic-pituitary function following childhood brain tumors: Analysis of prospective annual endocrine screening.

BACKGROUND: Outcomes for childhood brain tumors are now associated with a five-year survival rate of 75%. Endocrine effects of brain tumors are common, occurring in 43% of patients by 10 years from tumor diagnosis. Optimal timing of screening for endocrinopathies remains undefined. We aim to identify incidence and timing of endocrinopathies following brain tumor diagnosis, to better refine screening guidelines. METHODS: Retrospective chart review of patients referred to our hospital's neuro-oncology clinic for evaluation and treatment of brain tumors. Inclusion criteria were a positive history for brain tumor diagnosis and evaluation at our center. Data collection included demographics, tumor diagnosis, tumor therapy, and endocrinopathy diagnosis and timing. Laboratory data and clinical documentation were reviewed. RESULTS: Four hundred nineteen subjects were included for analysis. Tumor locations included supratentorial 158 (38%), posterior fossa 145 (35%), suprasellar 96 (23%), and upper spinal cord 20 (5%). Only 61% had undergone endocrine screening. Forty-five percent of screened patients had endocrinopathies. Endocrinopathy diagnosis typically occurred within six years after tumor diagnosis. Tumor recurrence and repeated therapies increased the risk for endocrinopathies within the subsequent six years after tumor therapy. Higher rates of endocrinopathies were identified in patients who had received cranial irradiation for posterior fossa, supratentorial, or suprasellar tumors. CONCLUSION: Endocrine screening should occur in childhood brain tumor survivors, particularly those who have received irradiation. Our study suggests that in children with brain tumors, the highest yield for finding a pituitary deficiency is within the first six years after tumor diagnosis and treatment. Screening should continue annually beyond six years, but with special attention in the subsequent six years after therapy for tumor recurrence. Prospective screening and endocrinology referral should be implemented in childhood brain tumor survivors.

Fertility preservation options in pediatric and adolescent patients with cancer.

The incidence of childhood cancer has steadily increased since the 1950s, with approximately 16,000 children diagnosed each year. However, with the advent of more effective multimodal therapies, childhood cancer survival rates have continued to improve over the past 40 years, with >80% of patients now surviving into adulthood. Fertility preservation (FP) has become an important quality-of-life issue for many survivors of childhood cancer. As a result, the therapeutic options have become less gonadotoxic over time and more patients are being offered FP options. This review examines the indications for consultation, male and female FP options both in the prepubertal patient and adolescent patient, and the unique ethical issues surrounding FP in this vulnerable population. Cancer 2018;124:1867-76. © 2018 American Cancer Society.

Viral surveillance using PCR during treatment of AML and ALL.

BACKGROUND: While viral surveillance of cytomegalovirus (CMV), Epstein-Barr virus (EBV), and adenovirus using PCR is routine in patients undergoing hematopoetic stem cell transplant and solid organ transplant, the utility in the nontransplant pediatric leukemia population is unknown. Our institution screens patients with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) for viral DNAemia by PCR as part of clinical care. PROCEDURE: This retrospective chart review included patients treated for newly diagnosed or relapsed AML or ALL between April 2010 and September 2014. We retrieved data for viral PCR screening, detection and quantification, duration of positivity, and prophylaxis or treatment. RESULTS: One hundred eleven patients were included in analyses. Forty (36.0%) had at least one blood PCR positive for EBV, CMV, or adenovirus. Patients with ALL had significantly higher rates of persistent viral detection and treatment than those with AML (P < 0.02, P < 0.01, respectively). International patients had significantly higher rates of viral detection (P < 0.01), persistence (P < 0.01), any treatment (P < 0.03), and antiviral treatment (P < 0.01); 16.9% of patients who received intravenous immunoglobulin (IVIG) prophylactically had viral detection compared to 63% of patients who did not receive prophylactic IVIG (P = 0.0008). CONCLUSIONS: Patients with ALL were more susceptible than those with AML to viral reactivation that was persistent or resulted in treatment. Patients with relapsed ALL, refractory ALL, or infantile ALL are most likely to benefit from asymptomatic screening for CMV and adenovirus. International patients are at higher risk for reactivation and may merit screening. EBV reactivation was not significant and does not warrant screening.

Examining decisional needs and contextual factors influencing fertility status assessment among young female survivors of childhood cancer: A sequential mixed methods study protocol.

INTRODUCTION: Female cancer survivors who received gonadotoxic cancer treatment are at risk for profound diminished ovarian reserve and/or primary ovarian insufficiency with resulting infertility, which can be associated with distress and decreased quality of life.. Despite prioritizing future parenthood, many survivors are unsure of the impact of their treatment on their future fertility, and little is known about the perceived reproductive health needs and factors associated with receipt of a fertility status assessment (FSA). There is a lack of developmentally appropriate reproductive health decisional support interventions available for emerging adult cancer survivors. This study will explore the perceived reproductive health needs of emerging adult female survivors of childhood cancer and to identify decisional and contextual factors that influence pursuit of FSA using an explanatory sequential quantitative to qualitative mixed methods design. METHODS AND ANALYSIS: This study will enroll 325 female survivors (aged 18 to 29 years and >1-year post treatment; diagnosed with cancer < age 21 years) from four cancer centers in the United States. Sociodemographic and developmental factors, reproductive knowledge and values, decisional needs, and receipt of an FSA will be assessed through a web-based survey. Informed by survey findings, a subset of participants will be recruited for qualitative interviews to explore decisional factors associated with uptake of an FSA. Clinical data will be abstracted from the medical records. Multivariable logistic regression models will be developed to identify factors associated with FSA and qualitative descriptive analysis will be used to develop themes from the interviews. Quantitative and qualitative findings will be merged using a joint display to develop integrated study conclusions and direct future interventional research.

Development of a Pediatric Fertility Preservation Program: A Report From the Pediatric Initiative Network of the Oncofertility Consortium.

Infertility is known to decrease quality of life among adults. In some cases, infertility is caused by medical conditions and/or treatments prescribed in childhood, and using methods to protect or preserve fertility may expand future reproductive possibilities. Structured programs to offer counseling about infertility risk and fertility preservation options are essential in the care of pediatric patients facing fertility-threatening conditions or treatments, yet multiple barriers to program development exist. This report was developed from the institutional experiences of members of the Pediatric Initiative Network of the Oncofertility Consortium, with the intent of providing guidance for health care providers aiming to establish programs at institutions lacking pediatric fertility preservation services. The mechanics of building a fertility preservation program are discussed, including essential team members, target populations, fertility preservation options (both established and experimental), survivorship issues, research opportunities, and ethical considerations. Common barriers to program development and utilization, including low referral rates and financial concerns, are also discussed, and recommendations made for overcoming such barriers.

Toxicity of Cancer Therapy in Adolescents and Young Adults (AYAs).

OBJECTIVES: To identify treatment-related toxicities that are either more frequent or more severe in the adolescent and young adult (AYA) oncology population. To explore differences in drug pharmacology and patient physiology that contribute to toxicities in the AYA population and to describe the impact of treatment-related toxicities on outcomes for AYA patients. DATA SOURCES: A PubMed search was undertaken using the key words Adolescent Young Adult Oncology, AYA, toxicity, bone marrow transplant, late effects, and chemotherapy. Additional toxicity information was also obtained from recent publications from cancer cooperative groups treating AYA patients. CONCLUSION: AYA patients often experience more severe toxicities than children when treated with identical chemotherapy regimens, which can interfere with successful administration of planned treatment, as well as have profound effects on quality of life. AYA patients with cancer face the dual challenge of disease biology associated with inferior response to treatment, thus necessitating treatment intensification, while at the same time suffering higher rates of specific toxicities such as vincristine-induced neuropathy, osteonecrosis, and treatment-related mortality caused by infection. IMPLICATIONS FOR NURSING PRACTICE: AYA patients are at a higher risk for toxicities from regimens that may be tolerated by younger patients. Staff should be aware of toxicities facing this population so that appropriate supportive care measures can be utilized. Future research on the pharmacology of drugs in adolescence, hormonal effects on drug-metabolizing enzymes, cumulative exposure to different drugs in combination, and risk and severity of specific toxicities will be critical to improving the treatment of AYA patients.

Attitudes regarding fertility preservation in female adolescent cancer patients.

Infertility is a devastating side effect of cancer treatment. Advances in fertility research have brought new preservation techniques to the forefront for women. The implication of this research in the field of pediatric oncology has not been reported. The objective of this study was to determine whether female adolescents with a diagnosis of cancer and their parents were interested in trying to preserve fertility. We conducted a cross-sectional survey of female patients, aged 10 to 21 years, and their parents. There were 39 parent/adolescent pair responses, 3 parent-only responses, and 8 adolescent-only responses. We found that adolescents and parents had thought about the future and were interested in research treatments to help preserve fertility, but not willing to postpone cancer therapy. Achieving a state of good health was most important to the adolescent group (P<0.001). There was no statistical difference between attitudes of parents and adolescents. In summary, parents and female adolescents are interested in options to help preserve fertility during cancer treatments, but they are not willing to postpone treatment for this purpose.