Management of Ependymoma in Children,Adolescents and Young Adults

Paediatric ependymomas are rare, malignant tumours arising throughout the central nervous system, but most frequently (in children) the posterior fossa. The standard of care for localised disease is gross total resection and focal radiotherapy, resulting in overall survival rates of up to 85%. Despite improvements in survival, treatment remains challenging, with persistently high rates of (rarely curable) relapse alongside risks of significant tumour and treatment-related toxicity. Systemic therapy is currently used to delay radiotherapy in very young children and in the management of metastatic or recurrent disease. Its use in the adjuvant setting is the subject of ongoing studies. Current research efforts are aimed at eliciting a better understanding of molecular biology, correlating this with tumour behaviour and defining targets for potential new agents. Prognosis seems to be related to the extent of surgical resection and the age at presentation. This article reviews clinical aspects of ependymoma management in children and young people.     

Humoral and Cellular Immunotherapy in ALL in Children,Adolescents, and Young Adults

Although the event-free survival for children and adolescents with acute lymphoblastic leukemia (ALL) has dramatically improved over the past half century, it has plateaued over the past decade. Children and adolescents with refractory/relapsed ALL continue to have a dismal prognosis with hematopoietic stem cell transplant being their most viable option for cure. There is an obvious need for the development of novel agents to further enhance overall outcomes. In this review we focus on the development of humoral and cellular immunotherapeutic agents in the treatment of childhood, adolescent, and young adult ALL. Immunotherapy in various forms has shown immense promise. To date we have seen numerous safety studies using monoclonal antibody therapy, antibody conjugates, bispecific T cell and bispecific natural killer (NK) cell antibodies and genetically reengineered T and NK cells expressing targeted chimeric antigen receptors. Initial success has been found with the anti-CD20 monoclonal antibodies followed by promising results using anti-CD22 and anti-CD19 therapies alone or in combination. Genetic modification of T and NK cells to express targeted chimeric antigen receptors offers a novel immunotherapy option that demonstrates enhanced cytotoxicity in otherwise resistant tumor cells. There is great potential to combine immunotherapies to further improve overall cure rates in children, adolescents, and young adults with poor-risk ALL. A number of humoral and cellular immunotherapy strategies have been investigated and found to be effective, safe, and well tolerated. Ideally, the targeted approach of immunotherapy will result in an overall decrease in toxicities experienced by patients. Future studies are required to determine when in the course of treatment with humoral and cellular therapy will have the safest and optimal effect in ALL.     

Four Ways to Decrease Late Toxicity From Pelvic Radiation Therapy in Children and Young Adults

The use of curative-intent multimodality therapy with chemotherapy, surgery, and radiation results in late toxicities in almost two-thirds of patients with pediatric cancer. When pelvic radiation is used for pediatric malignancies such as rhabdomyosarcoma, lymphoma, neuroblastoma, Ewing sarcoma, and Wilms tumor, the associated late toxicities can affect many normal tissues and may include growth asymmetries, cystitis, infertility, and sexual dysfunction. We describe 4 recommendations of how to prevent or minimize late toxicities from pelvic radiation and review the literature of these pediatric late toxicities.     

Treatment of Acute Lymphoblastic Leukemia in Adolescents and Young Adults

Treatment approaches for adolescents and young adults with acute lymphoblastic leukemia (ALL) have evolved considerably in the past 5–7 years. One of the major changes has been the widespread adoption of pediatric-based protocols, which appears to have significantly improved survival and probably renders allogeneic hematopoietic stem cell transplantation (HSCT) unnecessary in most standard-risk patients. However, high-risk patients, such as those with BCR-ABL or MLL rearrangements or high white count presentations, should still be referred for HSCT in CR-1. Minimal residual disease positivity has also been identified as a high-risk feature. Patients with BCR-ABL–positive ALL should receive combined therapy with a tyrosine kinase inhibitor and chemotherapy prior to HSCT. The adoption of pediatric-based regimens has been associated with significant additional toxicities, including venous thromboembolism, osteonecrosis, other steroid-related changes, and neuropathy, which can potentially have a major adverse impact on the quality of life of these young ALL patients.     

Incidence and Correlates of Radiation Dermatitis in Children and Adolescents Receiving Radiation Therapy for the Treatment of Paediatric Sarcomas

AimsTo investigate the relationship between the maximum grade of skin toxicity, radiation dose and clinical variables in children receiving treatment for sarcomas involving the bone and soft tissue.Materials and methodsBetween January 2003 and July 2006, 82 patients with musculoskeletal tumours on an Institutional Review Board (IRB)-approved prospective study at St. Jude Children's Research Hospital received three-dimensional conformal or intensity-modulated radiation therapy for local tumour control. Radiation dermatitis was graded according to the National Cancer Institute's Common Toxicity Criteria version 2.0 during and after radiation therapy. The dose to the skin was calculated for each patient from the radiation treatment plan.ResultsThe radiation doses delivered to the primary tumour ranged from 4140 to 7020cGy, with a mean dose of 5040cGy. The maximum recorded grade of skin toxicity was: grade 0: seven patients (8.6%); grade 1: 26 patients (31.7%); grade 2: 37 patients (45.1%); grade 3: 10 patients (12.2%); grade 4: two patients (2.4%). A significant association for increased grade of skin toxicity was observed between dose (P < 0.01), volume of skin treated above 4000cGy (P = 0.03), use of a bolus (P < 0.01), Caucasian race (P < 0.01) and related pain (P < 0.01).ConclusionsThese findings suggest that the delivered dose, use of a bolus, the volume treated, and race may be used in the clinical setting to predict patients at risk for skin toxicity. Alterations in treatment technique and early therapeutic intervention may help to reduce or eliminate radiation-induced skin side-effects and associated pain.     

The Treatment of Adolescents and Young Adults with Acute Lymphoblastic Leukemia

Adolescents and young adult (AYA) patients with acute lymphoblastic leukemia (ALL), 16–40 years of age, were historically not the focus of prospective studies on ALL treatment. This population has unique genetic, immunophenotypic, and clinical features, differing from both pediatric and older adult patients, with outcomes somewhere between these two populations. However, it has been suggested that outcomes (event-free and overall survival) for these patients are better when they are treated with pediatric-inspired therapeutic regimens. This has been attributed to increased dose and frequency of non-myelosuppressive therapy, earlier and more frequent central nervous system prophylaxis, and longer maintenance therapy. However, management by the treating oncologist and adherence by the patients are equally vital. Ultimately, the combination of improved treatment regimens and organizational management are required to improve outcomes of ALL in the AYA population.     

Improving Access to Standardized Fertility Preservation Information for Older Adolescents and Young Adults with Cancer: Using a User-Centered Approach with Young Adult Patients,Survivors, and Partners to Refine Fertility Knowledge Transfer

Adolescent and young adult (AYA) cancer patients under 40 should be made aware of their fertility risks and preservation options throughout their care. However, discussions on fertility preservation (FP) do not routinely occur. With a dearth of FP resources, oncology providers may lack knowledge around FP. Thus, informational needs can be unmet, leading to anxiety and distress in patients. Provision of pertinent and timely information can help patients cope better with their diagnosis. FP pamphlets were developed for men and women with cancer. A cross-sectional in-house survey, using convenience sampling, evaluated the pamphlets’ effectiveness and measured ease of understanding, acceptability, and perceived utility. Patients and partners were also asked to provide recommendations and complete the Short Test of Functional Health Literacy in Adults (S-TOFHLA) measuring health literacy level. This helps determine if health literacy influences perception of pamphlet effectiveness. All participants (n = 56) reviewed both pamphlets. Fifty-four participants (96 %) found the pamphlet for men useful, while 29 participants (52 %) improved their male fertility knowledge. The pamphlet for women was useful for 52 participants (93 %) and improved knowledge in 35 (63 %) of them. Although the majority of participants had adequate health literacy (98 %), there was insufficient sample diversity to determine if health literacy influenced the pamphlet’s effectiveness. Participants indicated preference in receiving verbal (73 %) and written (66 %) information over watching videos or in-class education. They recommended including fertility clinics, financial resources, and statistics in the brochures. These FP pamphlets were concluded as effective in supporting patients in making FP decisions.     

Comparison of Two Pediatric-Inspired Regimens to Hyper-CVAD in Hispanic Adolescents and Young Adults With Acute Lymphoblastic Leukemia

BackgroundPediatric-inspired regimens (PIR) in adolescents and young adults with acute lymphoblastic leukemia have led to better long-term outcomes. In Latin America, the adolescent and young adult population has an increasing incidence of acute lymphoblastic leukemia with poor outcomes (5-year OS of approximately 20%) with traditional regimens.Patients and MethodsA retrospective cohort study was performed of adolescent and young adult acute lymphoblastic leukemia patients treated with PIR in two reference centers in Mexico City between March 2016 and June 2019, in which the primary endpoint was OS, compared to a historic cohort of patients treated with hyper-CVAD treated between February 2009 and June 2015.ResultsWe compared 73 patients treated with PIR (46 and 27 received modified versions of the ALL-BFM 90 and CALGB C10403 regimens, respectively) and 173 patients treated with hyper-CVAD. Patients treated with PIR experienced higher 4-week complete response rates (79.5% vs. 64.2%; P = .02) and lower relapse rates (44.1% vs. 60.0%; P = .04). OS was significantly higher with PIR than with hyper-CVAD (24 months: 41.5% vs. 28.1%; P = .012). The benefit on OS for PIR was only significant for CALGB (24-month OS: 61.1% vs. 28.0%; P = .01) but not for BFM. In the multivariate analysis, hyperleukocytosis (hazard ratio [HR] = 1.90; 95% confidence interval [CI], 1.11-3.22; P = .02), autologous stem-cell transplantation (HR = 0.38; 95% CI, 0.17-0.86; P = .02), and 4-week complete response (HR = 0.43; 95% CI, 0.26-0.70; P < .01) were independent prognostic factors. For the group of patients older than 20 years, only CALGB had an independent prognostic factor for OS (HR = 0.44; 95% CI, 0.20-0.97; P = .04).ConclusionIn terms of 4-week complete response, relapse rates, and OS, PIR provides benefits to Hispanic patients.     

Three-dimensional Conformal Radiotherapy for Astrocytic Tumors Involving the Eloquent Area in Children and Young Adults

Purpose: Although a gross total removal of astrocytic tumors offers a favorable prognosis, it is often difficult to achieve in the eloquent area of the brain. This study was conducted to investigate the possible gain of three-dimensional conformal radiotherapy (3DCRT) for astrocytic tumors located in the eloquent area in children and young adults. Materials and methods: Twenty patients with astrocytic tumors received the radiotherapy. The median age was 17 years, ranging from 4 to 30 years. Fourteen low-grade tumors (seven pilocytic and seven diffuse), and six high-grade tumors (five anaplastic, one malignant pilocytic) were included. Tumors were located at the thalamus/hypothalamus in 12 cases, optic tract in one case, and the deep cerebral/cerebellar hemisphere in seven cases. A specific fixation device was used for 3DCRT. Forty-six Gy for low-grade tumors and 54 Gy for high-grade astrocytomas with 1.8–2.0 Gy per fraction were in principle employed as the standard regimen. Nominal radiotherapy fields ranged from 2.0 × 2.0 to 15.0 × 11.0 cm². The median follow-up period was 42 months, ranging from 3 to 108 months. Results: The actuarial survival rate at 5 years was 68% ±13% for all patients. The actuarial survival rate for low-grade glioma was 79% ± 14% at 5 years and 50% ± 20% at 3 years for high-grade glioma. The actual progression-free survival rate was 83% ± 11% at 5 years for low-grade glioma and 50% ± 20% for high-grade glioma. A complete response was obtained in three (21%) of 14 patients with low-grade astrocytic tumors. Two patients with low-grade tumors and four of six with high-grade tumors died due to tumor progression with in-field relapse but not marginal relapse. Twelve survivors with low-grade tumors showed no signs of relapse and no neurological, hormonal, or cognitive deterioration after radiotherapy and were able to attend their school or continue with a full-time job. Conclusions: 3DCRT is safe and effective for low-grade astrocytic tumors located in the eloquent area in children and young adults.     

Hypofractionated Stereotactic Ablative Radiotherapy for Recurrent or Oligometastatic Tumours in Children and Young Adults

AimsCancer remains a leading cause of death in children and adolescents in the developed world. Despite advances in oncological management, rates of primary treatment failure remain significant. Radiation of recurrent or metastatic disease improves survival in adults but there is little data to support clinical decision making in the paediatric/teenage and young adult population.Materials and methodsWe present a retrospective case series of 14 patients treated with stereotactic ablative body radiotherapy or stereotactic radiosurgery at The Royal Marsden Hospital from September 2011 to December 2015. Eligible patients were aged <25 years, with Lansky/Karnofsky performance status ≥60 with confirmed relapsed or metastatic tumour in fewer than three sites. Follow-up was in accordance with standard clinical care and included regular outpatient review and radiological surveillance. Local control, progression-free survival and overall survival are presented.ResultsData for 14 patients with 18 treated lesions were included. The median patient age was 15 years (range 5–20 years). Nine patients were treated for local recurrence and five for metastatic lesions. All patients had already undergone multiple previous treatments. Eleven patients had undergone previous radiotherapy. The median interval between the completion of initial radiotherapy and reirradiation was 29.0 months (range 0.2–49.5 months). The median follow-up was 3.4 years (range 0.28–6.4 years). The 1-year local control rate was 78.6% and the 2-year local control rate was 57.1%. Overall median survival was 58.4 months (95% confidence interval 33.8–82.9 months). Cumulative biologically effective doses (BED) over 200 Gy were associated with late toxicity (P = 0.04).ConclusionRadical doses of short-course hypofractionated radiotherapy can achieve excellent local control and may contribute to the prolongation of overall survival. There is a need for prospective trials exploring the use of ablative radiotherapy in metastatic disease in paediatric/teenage and young adult patients in order to establish safe and effective treatment schedules.     

Identifying and Addressing the Needs of Adolescents and Young Adults With Cancer: Summary of an Institute of Medicine Workshop

Cancer is the leading disease‐related cause of death in adolescents and young adults (AYAs). This population faces many short‐ and long‐term health and psychosocial consequences of cancer diagnosis and treatment, but many programs for cancer treatment, survivorship care, and psychosocial support do not focus on the specific needs of AYA cancer patients. Recognizing this health care disparity, the National Cancer Policy Forum of the Institute of Medicine convened a public workshop to examine the needs of AYA patients with cancer. Workshop participants identified many gaps and challenges in the care of AYA cancer patients and discussed potential strategies to address these needs. Suggestions included ways to improve access to care for AYAs, to deliver cancer care that better meets the medical and psychosocial needs of AYAs, to develop educational programs for providers who care for AYA cancer survivors, and to enhance the evidence base for AYAs with cancer by facilitating participation in research.     

How NCCN Guidelines Can Help Young Adults and Older Adolescents With Cancer and the Professionals Who Care for Them

From 1975 to 2009, adolescents and young adults with cancer in the United States had less mortality reduction and survival improvement than either children or older adults with cancer. An NCI Progress Review Group (PRG) convened in 2005 issued a variety of recommendations to overcome the lack of progress, including the establishment of care guidelines. The outcome of 15- to 39-year-olds with cancer in the United States in 2009 was ascertained from the SEER registry, and the first guidelines for this age group, presented by NCCN, were reviewed. For the first time, the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Adolescent and Young Adult Oncology provide specific algorithm-based care recommendations for 15- to 39-year-olds with cancer, who as an age group have the greatest potential patient-years of life to be saved. A special emphasis on psychosocial evaluation and care is included, commensurate with the unique needs of persons in this age group. Although how widely the NCCN Guidelines will be used remains to be seen, they are timely, comprehensive, responsive to the NCI PRG recommendations, and a valuable resource for medical oncologists, hematologists, gynecologic oncologists, oncologic surgeons, and pediatric oncologists who care for patients between 15 and 40 years of age. A patient version will have mutually beneficial effects for families and professionals.     

Outcome of Adolescents and Young Adults Compared With Pediatric Patients With Acute Myeloid and Promyelocytic Leukemia

BackgroundStudies on the outcome of adolescents and young adults (AYAs) with acute myeloid leukemia (AML) and acute promyelocytic leukemia (APL) are limited.MethodsWe compared the outcome of AYA (19-30 years) patients with AML and PML and pediatric (0-18 years) patients with AML (pAMLs) and APL (pAPLs) utilizing the Surveillance Epidemiology and End Results-18 registry. Early mortality rate (EMR), defined as mortality within 1 month of diagnosis, was used as a surrogate for treatment-related mortality. Survival statistics were computed using the Kaplan-Meier method. Multivariate analysis was done using logistic regression and the Cox proportional hazard regression model.ResultsA total of 6343 patients with AML were identified; 44.7% were AYAs. pAMLs had lower EMR (6.2% vs. 9.2%; P < .01) and higher overall survival (OS) (1-year, 70.3% vs. 62.1%; 5-year, 48.2% vs. 36.4%; P < .01). Nine hundred twenty patients with APL were also identified; 59.5% were AYAs. No statistically significant difference was found between AYAs with APL and pAPLs in EMR (11.4% vs. 14.1%; P = .23) and OS (1-year, 83.8% vs. 81.2%; P = .31 and 5-year, 68.2% vs. 73.1%; P = .11]. Comparing all patients with AML and APL, AYAs with APL and pAPLs had higher EMR (11.4% and 14.1% vs. 6.2% and 9.2%; P ≤ .01) but better OS than AYAs with AML and pAMLs (5-year OS, 68.2% and 73.1% vs. 48.2% and 36.4%; P ≤ .01).ConclusionOur analysis shows AYAs with AML have worse EMR and OS compared with pAMLs. AYAs with APL and pAPLs have similar outcomes. To our knowledge, this is the first study reporting outcomes of AYAs with APL and pAPLs using a large population-based registry and their comparison with same age patients with AML.