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 0.7 and 1.4 (acute lymphoblastic leukemia and cancers of the colorectum and testis). Eight cancers exhibited statistically significant decreases in incidence among AYAs: Kaposi sarcoma (KS), fibromatous neoplasms, melanoma, and cancers of the anorectum, bladder, uterine cervix, esophagus, and lung, each with an APC less than -1. AYAs had a higher proportion of noninvasive tumors than either older or younger patients. CONCLUSIONS: An examination of cancer incidence patterns in AYAs observed over the recent decade reveal a complex pattern. Thyroid cancer by itself accounts for most of the overall increase and is likely caused by overdiagnosis. Reductions in cervix and lung cancer, melanoma, and KS can be attributed to successful national prevention programs. A higher proportion of noninvasive tumors in AYAs than in children and older adults indicates a need to revise the current system of classifying tumors in this population.

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 82.5% (standard error, 0.2%). In AYAs, 14 cancers demonstrated evidence of a statistically significant improvement in their 5-year relative survival since 1992. Survival improved less in AYAs than in children for acute myeloid leukemia and medulloblastoma. Fourteen cancers had survival improvements that were found to be less in AYAs compared with older adults, including hepatic carcinoma, acute myeloid leukemia, high-grade astrocytoma, acute lymphocytic leukemia, pancreatic carcinoma, low-grade astrocytoma, gastric carcinoma, renal carcinoma, cancer of the oral cavity and pharynx, Hodgkin lymphoma, ovarian cancer, fibromatous sarcoma, other soft tissue sarcoma, and thyroid carcinoma. CONCLUSIONS: Improvements in the survival of several cancer types that occur frequently in AYAs are encouraging. However, survival does not appear to be improving to the same extent in AYAs as in children or older adults for several cancers. Further investment in exploring the distinct biology of tumors in this age group, and of their hosts, must be a priority in AYA oncology.

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. This report summarizes the findings from the workshop, opportunities to leverage existing data, and suggestions for future research priorities. Multidisciplinary teams that include basic scientists, epidemiologists, trialists, biostatisticians, clinicians, behavioral scientists, and health services researchers will be essential for future advances for AYAs with cancer.

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. Conclusions from this meeting included the need for basic biologic, genomic, and model development for AYA cancers as well as translational research studies to elucidate any fundamental differences between pediatric, AYA, and adult cancers. The biologic questions for future research are whether there are mutational or signaling pathway differences (for example, between adult and AYA colorectal cancer) that can be clinically exploited to develop novel therapies for treating AYA cancers and to develop companion diagnostics.

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. EXPERIMENTAL DESIGN: We evaluated the safety and pharmacokinetics of oral and i.v. vinorelbine administered weekly x 6 in children (age, 2-17 years) with different tumors. Patients with disease involvement in the bone marrow were eligible but were stratified and dose-escalated separately. Oral vinorelbine (week 1) was administered as liquid-filled gelatin capsules at thrice the i.v. dose. Intravenous vinorelbine doses of 24 to 37.5 mg/m(2) were administered on weeks 2 to 6. RESULTS: The dose-limiting toxicity in patients without marrow involvement was reversible neutropenia. Common nonhematologic toxicities included < or = grade 2 nausea/vomiting and increased hepatic transaminases. A higher mean i.v. Cl(TB) was observed (1.75 +/- 1.0 L/h/kg) compared with adult reports, with a mean t(1/2B) of 16.5 +/- 9.7 hours. Mean oral bioavailability was 28.5 +/- 22.5%. The apparent oral clearance (12.1 +/- 13.0 L/h/kg) and volume of distribution (69.4 +/- 30.6 L/kg) were substantially higher than in adults given similar oral doses. CONCLUSIONS: The maximum tolerated dose in children without bone marrow involvement was 30 mg/m(2), similar to that reported in adults, with myelosuppression being the dose-limiting toxicity. Higher plasma clearance resulted in lower area under the plasma concentration-time curves at a given dose compared with that reported in adults.

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.Breast cancer accounts for 40% of tumours in female AYAs and this age group includes the peak incidence of Hodgkin lymphoma. The late Professor Gianni Bonadonna contributed importantly to improved survival in patients with these two diseases. Accordingly, he would be justifiably proud of the advances in AYA oncology that are being made in Italy, especially the impact of his colleagues at the Istituto Nazionale dei Tumori (INT). The initiatives of the Associazione Italiana Ematologia Pediatrica and the Società Italiana Adolescenti con Malattie Onco-ematologiche are particularly noteworthy, with the accomplishment of productive collaboration between paediatric and adult cancer care providers serving as a model for other countries to emulate.Exporting these advances can be successful through the vehicle of "twinning": establishing sustainable cooperation between institutions in HICs and partners in LMICs. Colleagues in Monza and at INT have been leaders in such programmes for decades. Cancer in AYAs remains a global challenge to which Gianni Bonadonna surely would have risen with enthusiasm and leadership while securing measurable achievements.

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. However, patients treated with CRT had poorer performance on neurocognitive testing over time. CCG-134P evaluated the addition of intensified systemic and intrathecal therapy to VHD-MTX in 128 patients with high-risk acute lymphoblastic leukemia (ALL) and demonstrated reduced CNS relapse compared to the CCG-191P trial, but equivalent survival. CCG-144P compared VHD-MTX to IT-MTX alone in 175 patients with average-risk ALL and demonstrated equivalent survival. VHD-MTX was associated with significant toxicities, particularly neutropenia, transient hepatic dysfunction and sepsis. VHD-MTX achieved similar survival to other CNS-directed therapies without the long-term impact on intelligence, but with substantial acute toxicities.

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. Transport across the BBB relates to the neurovascular unit, which consists not only of endothelial cells but also of pericyte, glia, and neuronal elements.

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. OBSERVATIONS: Many of the challenges faced by AYAs with a diagnosis of malignant disease are shared by others with chronic medical conditions and even their healthy peers, such as a sense of invulnerability that may contribute to delays in diagnosis. A particular need for psychological support has been identified for AYAs with cancer, even after active therapy has been completed and especially in the context of palliative care. Notable needs also include fertility preservation and navigation through the multiple transitions in the cancer journey. Additionally, there is a "cost of cure." This is not only in the form of short-term, treatment-related morbidity and mortality but also in the burden of "late effects," including second cancers, that compromise quality of life and limit life expectancy. Establishing clinical programs devoted to AYAs with cancer, with complementary educational initiatives, will strengthen the advances made. It is anticipated that clinical trial accrual will increase substantially, providing further gains in survival. Likewise, addressing the challenges of survivorship, including secondary prevention of long-term morbidity and mortality, will lead to additional improvements in clinical outcomes. CONCLUSIONS AND RELEVANCE: Transferring this knowledge to the care of an estimated 1 million incident cases of cancer in AYAs worldwide, most of whom do not live in high-income countries, remains a considerable challenge.

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. In the long run, it may also help prevent cancer, at least among the country's older population. A realistic appraisal of the obstacles to the implementation of the ACA in the age group may compromise many of the desired outcomes, however. Nonetheless, ACA has provisions that should reduce the cancer problem in young adult Americans, some of which are now in effect and most of which will become available during the current decade.

Obesity and outcome in pediatric acute lymphoblastic leukemia.

PURPOSE: To evaluate the effect of obesity (defined as a body mass index > 95th percentile for age and sex at diagnosis) on outcome of pediatric acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: We retrospectively analyzed data from 4,260 patients with newly diagnosed ALL enrolled from 1988 to 1995 onto five concurrent Children's Cancer Group studies. Results were verified in a second cohort of 1,733 patients enrolled onto a sixth study from 1996 to 2002. RESULTS: The 1988 to 1995 cohort included 343 obese and 3,971 nonobese patients. The 5-year event-free survival rate and risk of relapse in obese versus nonobese patients were 72% +/- 2.4% v 77% +/- 0.6% (P = .02) and 26 +/- 2.4 v 20 +/- 0.6 (P = .02), respectively. After adjusting for other prognostic variables, obesity's hazard ratios (HRs) of events and relapses were 1.36 (95% CI, 1.04 to 1.77; P = .021) and 1.29 (95% CI, 1.02 to 1.56; P = .04), respectively. The effect of obesity was prominent in the 1,003 patients > or = 10 years old at diagnosis; in this subset, obesity's adjusted HRs of events and relapses were 1.5 (95% CI, 1.1 to 2.1; P = .009) and 1.5 (95% CI, 1.2 to 2.1; P = .013), respectively. In a second cohort of 1,160 patients 10 years old, obesity's adjusted HRs of events and relapses were 1.42 (95% CI, 1.03 to 1.96; P = .032) and 1.65 (95% CI, 1.13 to 2.41; P = .009), respectively. The effect of obesity on outcome was unrelated to changes in chemotherapy doses, length of intervals between chemotherapy cycles, or incidence and severity of therapy-related toxicity. CONCLUSION: Obesity at diagnosis independently predicts likelihood of relapse and cure in preteenagers and adolescents with ALL.

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. During the last 25 years, the incidence of cancer in this age range has increased faster while the increase in their cancer survival rates has been significantly lower than in younger or older patients, especially in comparison to results of the national pediatric cooperative cancer groups. Thus the 5-year outcome in 15-19 year olds with leukemias and sarcomas is not only worse than in younger patients, but also lower in this population at large than in patients of the same age treated at Children's Cancer Group institutions. In the United States, only approximately 5% of 15-25 year olds with cancer are entered onto clinical trials, in contrast to 60-65% of younger patients. Thus, cancer during adolescence and early adult life is an underestimated challenge that merits specific resources, solutions, and an international focus.

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. RESULTS: High achieving students engaged in extracurricular activities prior to diagnosis performed well academically in all three schooling situations. Those less engaged in school prior to diagnosis did poorly in homebound schools, better in their community schools, and best in the hospital school. CONCLUSIONS: Homebound learning during cancer therapy does not appear to be as meaningful as either hospital or community learning environments. Prior academic performance, as well as social, emotional, and health factors should be considered in selecting the most appropriate formal school environment for adolescent cancer patients.

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. Logistic regression analyses were performed to evaluate the association between high birth weight (>4,000 g) and occurrence of childhood cancer. RESULTS: Increased odds ratios (OR) were found for "total cancer cases" (OR 1.4, 95% CI 0.9-2.1), "leukemia cases" (OR 1.7, 95% CI 0.9-3.0) and "acute lymphoblastic leukemia (ALL) cases" (OR 2.2, 95% CI 1.2-4.1). Increased ORs in the former two groups were shown to be due to ALL cases. Including the race/ethnicity variable in the regression model did not affect the ORs. CONCLUSION: Compared to newborns who weighed between 2500 and 4000 g at birth, children who weighed >4,000 g had an increased risk of developing childhood ALL during the first five years of life. Birth weight differences does not explain the sequence of childhood cancer incidence by race/ethnicity.

Cancer in Adolescents and Young Adults

This is the first comprehensive book devotedexclusively to cancer in adolescents and young adults. First, anoverview of cancer in this age group, specifically from age 15 to29 inclusive, including epidemiology and the general differences inprevention, early detection, diagnosis and treatment are presented.Then, the 15 most common categories of cancers in the age groupregarding their epidemiologic, risk factors/etiology, presentingsymptoms and signs, diagnostic workup, treatment, survivaloutcomes, and adverse effects are each covered in separatechapters. The emphasis is on how the cancer in the age groupdiffers in epidemiology, biology, clinical management and outcomefrom the 'same' cancer in younger and older patients. Theindividual malignancies are followed by chapters on the generalpsychosocial, ethical and societal aspects of managing cancer inyoung adult and older adolescent patients. Model programs speciallydesigned to care for patients in the age group and surveillance oflong-term adverse effects are reviewed. This book should be ofinterest to practitioners, researchers and students in pediatriconcology, medical oncology, radiation oncology, surgical oncology,gynaecologic oncology, oncology nursing, social work, epidemiology,public health, and health services research.