A reflection on the work of Gianni Bonadonna from the viewpoint of the global challenge of adolescents and young adults with cancer.

Adolescents and young adults (AYAs - ages 15 to 39) constitute approximately 40% of the world's population and contribute an estimated one million new cases of cancer annually, the great majority in low- and middle-income countries (LMICs). In high-income countries (HICs) cancer is the commonest cause of disease-related death in AYAs, though overall 5-year survival rates now exceed 80%. A very different circumstance likely holds in LMICs, but accurate assessments are not readily available.

Cancer in Adolescents and Young Adults: A Narrative Review of the Current Status and a View of the Future.

Importance: Although cancer remains the most common cause of disease-related death in adolescents and young adults (AYAs) in high-income countries, their overall survival rates continue to increase and now exceed 80% at 5 years in several high-income countries. This has been accomplished through progressive improvements in active treatment and supportive care, although accrual rates to therapeutic clinical trials remain disappointing. Recognition of the unique distribution of diseases in the AYA population with cancer and further understanding of the distinctive biology of cancers in AYAs will lead to continuing gains in clinical outcomes.

Biologic and clinical characteristics of adolescent and young adult cancers: Acute lymphoblastic leukemia, colorectal cancer, breast cancer, melanoma, and sarcoma.

Adolescent and young adult (AYA) patients with cancer have not attained the same improvements in overall survival as either younger children or older adults. One possible reason for this disparity may be that the AYA cancers exhibit unique biologic characteristics, resulting in differences in clinical and treatment resistance behaviors. This report from the biologic component of the jointly sponsored National Cancer Institute and LiveStrong Foundation workshop entitled "Next Steps in Adolescent and Young Adult Oncology" summarizes the current status of biologic and translational research progress for 5 AYA cancers; colorectal cancer breast cancer, acute lymphoblastic leukemia, melanoma, and sarcoma.

Next steps for adolescent and young adult oncology workshop: An update on progress and recommendations for the future.

Each year, 70,000 adolescents and young adults (AYAs) between ages 15 and 39 years in the United States are diagnosed with cancer. In 2006, a National Cancer Institute (NCI) Progress Review Group (PRG) examined the state of science associated with cancer among AYAs. To assess the impact of the PRG and examine the current state of AYA oncology research, the NCI, with support from the LIVESTRONG Foundation, sponsored a workshop entitled "Next Steps in Adolescent and Young Adult Oncology" on September 16 and 17, 2013, in Bethesda, Maryland.

Comparison of cancer survival trends in the United States of adolescents and young adults with those in children and older adults.

Background: With prior reports indicating a lack of progress in survival improvement in older adolescents and young adults (AYAs) aged 15 to 39 years with cancer compared with both younger and older patients with cancer, the current analysis provides an update of survival trends of cancers among AYAs, children, and older adults.

Methods: Data from the National Cancer Institute Surveillance, Epidemiology, and End Results database for 13 regions were used to ascertain survival trends of the 34 most frequent cancers diagnosed in AYAs compared with children and older adults.

Results: As of 2002 through 2006, the 5-year relative survival rate for all invasive cancers in AYAs was 82.

Incidence and incidence trends of the most frequent cancers in adolescent and young adult Americans, including "nonmalignant/noninvasive" tumors.

Background: Incidence rates and trends of cancers in adolescents and young adults (AYAs) ages 15 to 39 years were reexamined a decade after the US National Cancer Institute AYA Oncology Progress Review Group was established.

Methods: Data from the Surveillance, Epidemiology, and End Results program through 2011 were used to ascertain incidence trends since the year 2000 of the 40 most frequent cancers in AYAs, including tumors with nonmalignant/noninvasive behavior.

Results: Seven cancers in AYAs exhibited an overall increase in incidence; in 4, the annual percent change (APC) exceeded 3 (kidney, thyroid, uterus [corpus], and prostate cancer); whereas, in 3, the APC was between 0.

Potential favorable impact of the affordable care act of 2010 on cancer in young adults in the United States.

On September 23, 2010, as a result of the Affordable Care Act (ACA), young adults throughout the United States younger than 26 years were required, with few exceptions, to have health insurance for the first time under a parent's insurance if the policy allows for dependent coverage. The ACA also provides for elimination of coverage denial for having had a previous diagnosis of cancer or other preexisting conditions as a result of the cancer and its therapy, provision of a minimum health benefits package including preventive services and professional counseling for obesity, alcohol and substance dependence, physical activity, and nutrition improvement. How these changes and the multiple other provisions of the ACA will affect young adults during the next decade is uncertain, but it has the potential to lead to earlier diagnosis of cancer, less invasive cancer therapy, better quality of survival, and higher cure rates.

Very high-dose methotrexate (33.6 g/m(2)) as central nervous system preventive therapy for childhood acute lymphoblastic leukemia: results of National Cancer Institute/Children's Cancer Group trials CCG-191P, CCG-134P and CCG-144P.

Between 1977 and 1991, the Children's Cancer Group and the National Cancer Institute conducted three trials of very high-dose methotrexate (33.6 g/m2; VHD-MTX) in place of cranial radiation (CRT) as central nervous system (CNS) preventive therapy, and assessed efficacy, acute toxicity and long-term neurocognitive outcome. CCG-191P compared VHD-MTX to CRT plus intrathecal methotrexate (IT-MTX) in 181 patients and demonstrated equivalent survival.

Phase I evaluation of oral and intravenous vinorelbine in pediatric cancer patients: a report from the Children's Oncology Group.

Purpose: Vinorelbine (Navelbine) is an orally absorbable Vinca with broad antitumor activity. It differs from other Vinca in that it is structurally modified on the catharanthine nucleus and has differential actions on tubulin that render it less neurotoxic than other compounds in this class. We conducted a phase I study of vinorelbine given the activity of Vinca alkaloids in many pediatric tumors.

New frontiers in translational research in neuro-oncology and the blood-brain barrier: report of the tenth annual Blood-Brain Barrier Disruption Consortium Meeting.

The blood-brain barrier (BBB) presents a major obstacle to the treatment of malignant brain tumors and other central nervous system (CNS) diseases. For this reason, a meeting partially funded by an NIH R13 grant was convened to discuss recent advances and future directions in translational research in neuro-oncology and the BBB. Cell biology and transport across the BBB, delivery of agents to the CNS, neuroimaging, angiogenesis, immunotherapy, and gene therapy, as well as glioma, primary CNS lymphoma, and metastases to the CNS were discussed.

The management of cancer in the older adolescent.

Cancer in adolescents 15-19 years of age occurs at nearly twice the rate observed in 5- to 14-year-olds, but as of yet they have no explicit organisation for research and care, such as that structured for younger paediatric patients. Adolescents with cancer must be recognised as a subgroup of oncology patients with specific characteristics and needs requiring dedicated interest and management. The need is made most evident as outcome data indicates that adolescents are lagging behind in survival gains made in recent decades by both children and adults with cancer.

Homebound schooling is the least favorable option for continued education of adolescent cancer patients: a preliminary report.

Background: With an overall objective to improve the educational programs of pediatric cancer patients, the purpose of this study was to compare the quality of educational experiences of adolescent cancer patients undergoing treatment while enrolled in hospital, homebound, or community schools.

Procedure: Ten students, 12-17 years of age at diagnosis, their parent and their teachers were interviewed with a structured list of open-ended questions designed to assess their perceptions of their homebound, hospital, and community school experiences. The interviews were taped, transcribed, and analyzed using qualitative methods for recurring themes.

Birth weight, ethnicity, and occurrence of cancer in children: a population-based, incident case-control study in the State of Texas, USA.

Objective: To investigate the relationship between birth weight and risk of early age childhood cancer and whether racial differences in birth weight distribution could explain differences in the incidence of cancer in white, Hispanic, and black children.

Methods: We compared birth weights of 268 children younger than five years old and diagnosed with cancer in the State of Texas in 1995 to the birth weights of 2680 randomly selected, age-matched population-based controls. Birth weight, sex, race/ethnicity, maternal age, smoking status, parity, and gestational age information was ascertained from the birth certificates.

Cancer in older adolescents and young adults: epidemiology, diagnosis, treatment, survival, and importance of clinical trials.

Cancer in adolescents and young adults has unique features in addition to the special medical, physical, psychological, and social needs of patients in this age group. The spectrum of malignant diseases is different from that in any other period in life, and it is strikingly different from the pattern in older persons. More people 15-25 years of age are diagnosed to have cancer than during the first 15 years of life.

Importance of dose intensity in neuro-oncology clinical trials: summary report of the Sixth Annual Meeting of the Blood-Brain Barrier Disruption Consortium.

Therapeutic options for the treatment of malignant brain tumors have been limited, in part, because of the presence of the blood-brain barrier. For this reason, the Sixth Annual Meeting of the Blood-Brain Barrier Disruption Consortium, the focus of which was the "Importance of Dose Intensity in Neuro-Oncology Clinical Trials," was convened in April 2000, at Government Camp, Mount Hood, Oregon. This meeting, which was supported by the National Cancer Institute, the National Institute of Neurological Disorders and Stroke, and the National Institute of Deafness and Other Communication Disorders, brought together clinicians and basic scientists from across the U.

Children's Cancer Group trials in childhood acute lymphoblastic leukemia: 1983-1995.

Since 1968, the Children's Cancer Group (CCG) has treated more than 16,000 children with acute lymphoblastic leukemia (ALL). Herein, we report improvements obtained in CCG trials during two successive series of studies (1983-1988 and 1989-1995). Overall, 10-year EFS was 62% +/- 10% for the 1983-1988 series and 72% +/- 1% for the 1988-1995 series (P< 0.

Oral cancer chemotherapy in paediatric patients: obstacles and potential for development and utilisation.

Although most cancer chemotherapy in children is administered parenterally, oral formulations are becoming increasingly available for use in patients as young as infants. Incentives for this approach include safety, flexibility, reduced financial cost, improved quality of life, and the potential for improved efficacy. The ability to deliver chemotherapy at home and apply schedules of administration that increase the agent's efficacy because patients do not require hospitalisation or visits to the clinic renders oral chemotherapy particularly attractive.

Epidemiologic impact of children with brain tumors.

The impact of CNS tumors during childhood and adolescence has been steadily increasing. In many countries, brain and spinal cord tumors are now second in frequency only to leukemia as a cancer affecting children, and the most common cause of cancer mortality in the young. In the United States, brain tumors are now more common than acute lymphoblastic leukemia, and the proportion of cancer deaths due to CNS tumors has nearly doubled during the past 25 years.

Pharmacokinetics and pharmacodynamics of oral methotrexate and mercaptopurine in children with lower risk acute lymphoblastic leukemia: a joint children's cancer group and pediatric oncology branch study.

We prospectively assessed the pharmacokinetics of methotrexate, mercaptopurine, and erythrocyte thioguanine nucleotide levels in a homogenous population of children with lower risk acute lymphoblastic leukemia and correlated pharmacokinetic parameters with disease outcome. The maintenance therapy regimen included daily oral mercaptopurine (75 mg/m2) and weekly oral methotrexate (20 mg/m2). One hundred ninety-one methotrexate doses and 190 mercaptopurine doses were monitored in 89 patients.