Archie Bleyer

The distinctive biology of cancer in adolescents and young adults

One explanation for the relative lack of progress in treating cancer in adolescents and young adults is that the biology of malignant diseases in this age group is different than in younger and older persons, not only in the spectrum of cancers but also within individual cancer types and within the patient (host). Molecular, epidemiological and therapeutic outcome comparisons offer clues to this distinctiveness in most of the common cancers of adolescents and young adults. Translational and clinical research should not assume that the biology of cancers and patients is the same as in other age groups, and treatment strategies should be tailored to the differences.

Breast Cancer Before Age 40 Years

Approximately 7% of women with breast cancer are diagnosed before the age of 40 years, and this disease accounts for more than 40% of all cancer in women in this age group. Survival rates are worse when compared to those in older women, and multivariate analysis has shown younger age to be an independent predictor of adverse outcome. Inherited syndromes, specifically BRCA1 and BRCA2, must be considered when developing treatment algorithms for younger women. Chemotherapy, endocrine, and local therapies have the potential to significantly impact both the physiologic health-including future fertility, premature menopause, and bone health-and the psychological health of young women as they face a diagnosis of breast cancer.

Adolescents and young adults with cancer : The scope of the problem and criticality of clinical trials

In the U.S., older adolescents and young adults with cancer have benefited less from therapeutic advances than did either younger or older patients. One factor that may explain this deficit is the relative lack of participation of patients in this age group on clinical trials of therapies that could improve their outcome. Comparisons were made of the participation of cancer patients on clinical trials in the U.S., as a function of patient age, with the change in national cancer mortality rate; and Surveillance, Epidemiology, End Results (SEER) cancer survival rate as a function of age. The participation rate in cancer treatment trials has been strikingly lower in 15–34‐year‐olds than in younger or older patients. The nadir has been apparent for both males and females in all of the major ethnic and racial groups. The national cancer mortality reduction and SEER survival improvement shows a similar age dependence. In the U.S., the age‐dependence of cancer treatment trial participation, and of improvement in survival prolongation and cancer death rates, are correlated. Regardless of whether there is a causal relationship, the impact on the older adolescent and young adult U.S. population is substantial, adversely affecting the national cost of healthcare, the person‐years of life lost, the loss of young people entering the job market, and the scientific knowledge and social implications of cancer during adolescence and early adulthood. National initiatives are underway to address these issues, with special emphasis on increasing the availability and access to clinical trials designed for older adolescents and young adults. Cancer 2006.

Improved disease-free survival of children with acute lymphoblastic leukemia at high risk for early relapse with the New York regimen--a new intensive therapy protocol: a report from the Childrens Cancer Study Group.

An intensive multimodal therapy was developed for the treatment of a subpopulation of children with acute lymphoblastic leukemia (ALL) who had a predicted event-free survival of less than 40% on previously reported therapeutic regimens (at high risk for early relapse). Induction with multiagent chemotherapy and radiotherapy to bulky disease-bearing areas (peripheral lymph nodes and mediastinum) was followed by consolidation, CNS prophylaxis, and cyclical remission maintenance therapy. Ninety-six (96%) of 100 previously untreated patients, 1 to 17 years of age, attained a complete remission. Seven patients received other maintenance therapy or a bone marrow transplant in remission. Sixty-six of the remaining 89 (74%) are in continuous complete remission at 22+ to 72+ months (median, 44+ months). Marrow relapse occurred in 15 (17%), CNS relapse in 5 (6%), and testicular relapse in one. Sixty-six of the 93 evaluable patients (71%) (including the induction failures) are event-free survivors. Two patients died of infection during the induction phase. No patient died during consolidation or maintenance without recurrent disease. The patients spent a median of 19, 0, and 0 days hospitalized during induction, consolidation, and maintenance, respectively. The most common complications were bacteremia and mucositis during induction and mucositis and fever during periods of neutropenia in consolidation. Maintenance was well tolerated. We conclude that the treatment protocol is intensive, but the inherent toxicities are manageable with adequate supportive care. The life table--projected event-free survival of 69% +/- 5% 48 months from diagnosis is encouraging.

Assessing the health care needs of adolescent and young adult cancer patients and survivors

Improvements in cancer outcomes observed for the United States population as a whole are not experienced as such by adolescent and young adult (AYA) patients. The objective of this study was to identify important health and supportive care needs for AYA patients and survivors.

Incidence of Breast Cancer With Distant Involvement Among Women in the United States, 1976 to 2009

IMPORTANCE Evidence from the US National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) database suggests that the incidence of advanced breast cancer in young women is increasing. OBJECTIVE To quantify this trend and analyze it as a function of stage at diagnosis, race/ethnicity, residence, and hormone receptor status. DESIGN, SETTING, AND PATIENTS Breast cancer incidence, incidence trends, and survival rates as a function of age and extent of disease at diagnosis were obtained from 3 SEER registries that provide data spanning 1973-2009, 1992-2009, and 2000-2009. SEER defines localized as disease confined to the breast, regional to contiguous and adjacent organ spread (eg, lymph nodes, chest wall), and distant disease to remote metastases (bone, brain, lung, etc). MAIN OUTCOME MEASURE Breast cancer incidence trends in the United States. RESULTS In the United States, the incidence of breast cancer with distant involvement at diagnosis increased in 25- to 39-year-old women from 1.53 (95% CI, 1.01 to 2.21) per 100,000 in 1976 to 2.90 (95% CI, 2.31 to 3.59) per 100,000 in 2009. This is an absolute difference of 1.37 per 100,000, representing an average compounded increase of 2.07% per year (95% CI, 1.57% to 2.58%; P < .001) over the 34-year interval. No other age group or extent-of-disease subgroup of the same age range had a similar increase. For 25- to 39-year-olds, there was an increased incidence in distant disease among all races and ethnicities evaluated, especially non-Hispanic white and African American, and this occurred in both metropolitan and nonmetropolitan areas. Incidence for women with estrogen receptor-positive subtypes increased more than for women with estrogen receptor-negative subtypes. CONCLUSION AND RELEVANCE Based on SEER data, there was a small but statistically significant increase in the incidence of breast cancer with distant involvement in the United States between 1976 and 2009 for women aged 25 to 39 years, without a corresponding increase in older women.

National survival trends of young adults with sarcoma: lack of progress is associated with lack of clinical trial participation.

Young adults with cancer in the U.S. have had less improvement in survival than either younger patients or older patients. The authors attempted to determine whether similar deficits have occurred in young adults with sarcomas and, if so, then why.

The challenges of clinical trials for adolescents and young adults with cancer.

In the United States, Europe, and Australia, and probably all countries of the world, older adolescents and young adults with cancer are under‐represented in clinical trials of therapies that could improve their outcome. Simultaneously, the survival and mortality rates in these patients have mirrored the clinical trial accrual pattern, with little improvement compared with younger and older patients. This suggests that the relative lack of participation of adolescent and young adult patients in clinical trials has lessened their chances for as good an outcome as that enjoyed by patients in other age groups. Thus, increased availability of and participation in clinical trials is of paramount important if the current deficits in outcome in young adults and older adolescents are to be eliminated. Regardless of whether there is a causal relationship, the impact of low clinical trial activity on furthering our scientific knowledge and management of cancer during adolescence and early adulthood is detrimental. Pediatr Blood Cancer 2008:50:1101–1104.

Prevention and management of asparaginase/pegasparaginase- associated toxicities in adults and older adolescents: recommendations of an expert panel

Abstract The rapidly increasing use of pegasparaginase (pegASNase) in adults, after a half century of use of asparaginase (ASNase) in children, has prompted a need for guidelines in the management and prevention of toxicities of asparagine depletion in adults. Accordingly, an initial set of recommendations are provided herein. Major advantages of pegASNase are its 2–3-week duration of action, in contrast to less than 3 days with native ASNase, and the flexibility of intravenous or intramuscular administration of pegASNase and associated patient and physician convenience. The most frequent toxicities of both types of ASNase are hepatic and pancreatic, with pancreatitis being the most serious. Other toxicities are hypersensitivity reactions, thrombosis, nausea/vomiting, and fatigue. Whether or not the replacement of one dose of pegASNase for 6–9 doses of native ASNase can be achieved in adults with similar efficacy and acceptable toxicities to those achieved in children remains to be established.

Cancer in Young Adults 20 to 39 Years of Age: Overview

Among 20- to 39-year-olds, cancer causes more deaths than any other disease except depression that culminates in suicide. More females in the age group die of cancer than of the next three causes combined. Yet, substantially less attention has been given to young adults than to children and older adults, and the relative improvement in the survival rate in young adults has not kept pace with that achieved in younger or older patients. Additionally, there is evidence that a substantial proportion of the cancers in young adults have a different biology, and probably etiology/pathogenesis, than that of what appears to be the same cancer in younger or older persons. The challenges of early detection, diagnosis, treatment, and follow-up are therefore likely to be distinctly different than in persons of a different age. As an introduction to this Seminars in Oncology issue on young adults with malignant disease, this overview summarizes cancer epidemiology, risk factors, survival, racial/ethnic and gender differences, diagnostic and treatment approaches, psychosocial challenges, and current organizational research and supportive care strategies in young adults.