IMPORTANCE Previous studies have demonstrated that adolescents and young adults (AYAs) with cance... more IMPORTANCE Previous studies have demonstrated that adolescents and young adults (AYAs) with cancer are a distinct cancer population; however, research on long-term epidemiological trends and characteristics of cancers in AYAs is lacking. OBJECTIVE To characterize the epidemiology of cancer in AYAs aged 15 to 39 years with respect to (1) patient demographic characteristics, (2) frequencies of cancer types, and (3) cancer incidence trends over time. DESIGN, SETTING, AND PARTICIPANTS This retrospective, serial cross-sectional, populationbased study used registry data from the Surveillance, Epidemiology, and End Results (SEER) database from January 1, 1973, to December 31, 2015 (SEER 9 and SEER 18). The study population was from geographically distinct US regions, chosen to represent the racial and ethnic heterogeneity of the country. Initial analyses were performed from January 1 to August 31, 2019. MAIN OUTCOMES AND MEASURES Incidence rates and descriptive epidemiological statistics for patients aged 15 to 39 years with invasive cancer. RESULTS A total of 497 452 AYAs diagnosed from 1973 to 2015 were included in this study, with 293 848 (59.1%) female and 397 295 (79.9%) White participants. As AYAs aged, an increase in the relative incidence of carcinomas and decrease in the relative incidence of leukemias, lymphomas, germ cell and trophoblastic neoplasms, and neoplasms of the central nervous system occurred. Among the female AYAs, 72 564 (24.7%) were diagnosed with breast carcinoma; 48 865 (16.6%), thyroid carcinoma; and 33 828 (11.5%), cervix and uterus carcinoma. Among the male AYAs, 37 597 (18.5%) were diagnosed with testicular cancer; 20 850 (10.2%), melanoma; and 19 532 (9.6%), non-Hodgkin lymphoma. The rate of cancer in AYAs increased by 29.6% from 1973 to 2015, with a mean annual percentage change (APC) per 100 000 persons of 0.537 (95% CI, 0.426-0.648; P < .001). Kidney carcinoma increased at the greatest rate for both male (APC, 3.572; 95% CI, 3.049-4.097; P < .001) and female (APC, 3.632; 95% CI, 3.105-4.162; P < .001) AYAs. CONCLUSIONS AND RELEVANCE In this cross-sectional, US population-based study, cancer in AYAs was shown to have a unique epidemiological pattern and is a growing health concern, with many cancer subtypes having increased in incidence from 1973 to 2015. Continued research on AYA cancers is important to understanding and addressing the distinct health concerns of this population.
The efficacy of asparaginase in acute lymphoblastic leukemia (ALL) is dependent on depletion of a... more The efficacy of asparaginase in acute lymphoblastic leukemia (ALL) is dependent on depletion of asparagine, an essential amino acid for ALL cells. The target level of plasma asparaginase activity to achieve asparagine depletion has been between 0.05-0.4 IU/mL. COG AALL07P4 examined the asparaginase activity and plasma and CSF asparagine concentration of pegaspargase when given intravenously in the treatment of NCI high risk ALL. Matched plasma asparaginase/ asparagine levels of the clearance of 54 doses of pegaspargase given in induction or consolidation demonstrated that all patients who had a plasma asparaginase level >0.02 IU/mL had undetectable plasma asparagine. No difference was observed in CSF asparagine levels associated with matched plasma asparaginase levels of 0.02-0.05 vs. 0.05-0.22 IU/mL (p=0.25). Our data suggest that a plasma asparaginase activity level of 0.02 IU/mL can effectively deplete plasma asparagine. The data also indicate that the 95%CI for plasma asparagine depletion after a pegaspargase dose is 22-29 days.
Inclusion in cancer clinical trials is considered the optimal standard of care, offering improved... more Inclusion in cancer clinical trials is considered the optimal standard of care, offering improved patient experience and progressive survival gains for subsequent generations of patients. Adolescent and young adult (AYA) patients are underrepresented in cancer research; consequently, improvements in outcomes for AYAs lag behind their pediatric and adult counterparts. Despite international evidence of underrepresentation in research, systematically tested interventions to improve recruitment for AYAs do not exist, and recruitment rates for AYAs continue to be lower than those for children. We review recruitment of AYAs into trials and discuss barriers and facilitators.
This book, arranged in an MCQ format complemented by oral exam questions, is designed to meet the... more This book, arranged in an MCQ format complemented by oral exam questions, is designed to meet the needs of a wide range of examinees. Essential aspects of radiation physics, radiobiology, and clinical radiation oncology are well covered. Tumors at different sites are addressed in a series of individual chapters, and further chapters are devoted to lymphomas and total body irradiation, pediatric tumors, and rare tumors and benign diseases. The answer keys provide clear explanations for both the correct answers and incorrect statements.
Investigating the potential biological basis of age-related differences in outcome for AYA with c... more Investigating the potential biological basis of age-related differences in outcome for AYA with cancer could lead to a better understanding of the biology, facilitate the development of new diagnostic and predictive markers, and identify novel therapeutic targets and treatment approaches for AYA patients. The evidence that cancers in AYA patients may differ biologically from those in older and younger populations includes data from numerous laboratories. However, much of this evidence is preliminary, and large comprehensive studies to confirm and validate these findings are only now beginning to get underway. Indeed, there may be substantial differences in biological and molecular features between different age groups even within the population of AYA patients with a specific cancer type. If age is a good surrogate for a unique tumor biology associated with AYA cancers, then studies of cancers in AYA patients will almost certainly illuminate alternative tumorigenic pathways and will also likely benefit patients in other age groups whose tumors exhibit similar biological/molecular features. The biologic, molecular, and clinical features of five AYA cancers (colon, breast, acute lymphoblastic leukemia, melanoma, and sarcoma) are highlighted in this chapter, and the current state of research for each of them is examined. What will be required to better diagnose, treat, and predict response in patients with AYA cancer is also discussed.
While the epidemiology of cancer has been studied in children and older adults for more than a ha... more While the epidemiology of cancer has been studied in children and older adults for more than a half century, little attention had been paid to the cancers in between those that occur in the older adolescents and young adult (AYA) between 15 and 40 years of age. Yet as recently ascertained, more than a million new cases of invasive cancer are diagnosed in AYAs annually worldwide. Not only are the array of cancers that are diagnosed in AYAs unique, accumulating evidence suggests that many are biologically distinct from what appears to be the same neoplasm in younger and older persons. AYA cancers may thereby have different etiologies and require different therapeutic strategies. Many cancers peak in incidence in AYAs, and there is an intermediate peak between the well-known childhood cancer peak and the predominant one that occurs in the elderly. If the cancers that account for the childhood peak are embryonal/fetal cancers and those that account for the peak late in life as the cancers of aging, the AYA peak may be considered as due to cancers of intermediate growth and maturation. For most of the past quarter century, the incidence of the AYA cancers has been increasing for reasons that have not been ascertained. In Europe, the United States, and Japan, the 5-year survival rates of the vast majority of cancers in AYA have been remarkably similar. In the United States, the overall rate of survival improvement had been less in AYAs than in either younger or older patients. The trends and patterns of incidence do offer certain clues as to cancer causation in AYAs and potential methods of prevention. Detailed analyses of incidence patterns by geographic region and demographic factors together with determination of variations in incidence in time and space should provide additional insights into etiology and separate lines of investigation and therapeutic opportunities.
After a half century of clinical trials, expansive observations, vigorous advocacy and debate, sc... more After a half century of clinical trials, expansive observations, vigorous advocacy and debate, screening mammography could not be in a more controversial condition, especially the potential harm of overdiagnosis. Despite a simple rationale (catch the cancer early and either prevent death or at least decrease the amount of therapy needed for cure), the estimates to date of overdiagnosis rates are conflicting and the interpretations complex. Since the author&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s 2012 publication in the New England Journal of Medicine (NEJM), the peer-reviewed publications on overdiagnosis caused by screening mammography are reviewed and the NEJM analyses updated with three additional calendar years of results. The recent peer-reviewed medical literature on screening mammography induced overdiagnosis of breast cancer has increased exponentially, nearly 10-fold in 10 years. The average estimate of overdiagnosis is about 30%, but the range extends from 0% to 70+%. An update of the NEJM report estimates that in the US, 78,000 women and 30%-31% of those diagnosed with breast cancer at the age of 40 years or older during 2011 were overdiagnosed. Until we have better screening procedures that identify who really has cancer and needs to be treated, the risk of overdiagnosis relative to the benefit of screening merits more effective public and professional education. Radiologists, pathologists, and other professionals involved with screening mammography should recognize that the potential harm of overdiagnosis is downplayed or not discussed with the patient and family, despite agreement that the objective is informed choice.
Despite the increase in thyroid cancer incidence among adolescents and young adults (AYAs), this ... more Despite the increase in thyroid cancer incidence among adolescents and young adults (AYAs), this group has received limited attention. We reviewed the epidemiology and challenges of thyroid cancer care among AYAs, and proposed a research agenda to improve their care. Thyroid cancer is the most common cancer in American adults 16-33 years of age. AYAs with thyroid cancer face challenges including overdiagnosis reduced healthcare access and inconsistent care. Successful treatment of these patients results in additional challenges due to ongoing side effects of treatment as well as lasting impacts on their quality of life. These challenges should fuel a collaborative research agenda aimed at improving the quality of care for AYAs with thyroid cancer across the spectrum of diagnosis, treatment and survivorship.
Background: Hodgkin lymphoma (HL) is one of the most common, and one of the most curable cancers ... more Background: Hodgkin lymphoma (HL) is one of the most common, and one of the most curable cancers in adolescents and young adults (AYAs) (15-39 years). Despite excellent outcomes in the majority of patients, the burden of long-term morbidity and mortality persists. Prior analyses of patients treated for HL before the year 2000 have reported mortality rates as high as 30% by 20 years. Further, this mortality risk has historically differed across different racial and ethnic groups. Over the past decade, cooperative groups have expanded the use of risk-adapted, response-based treatment in an effort to maintain high cure rates, while simultaneously reducing the burden of late effects. We examined long-term survival in AYAs with HL treated after the year 2000. Methods: We used the National Cancer Institute Surveillance, Epidemiology, and End Results registry data for 18 regions in the United States (SEER18) to examine survival in AYAs with a confirmed diagnosis of HL between 2000 and 2015. We obtained overall and cause-specific survival estimates for each year after cancer diagnosis (up to 15 years) for each racial/ethnic group with corresponding 95% confidence intervals. From these yearly survival estimates, we calculated the percentage of deaths not attributed to HL at 10- and 15-years after cancer diagnosis. Results: The final analysis included 16,868 HL patients. Racial/ethnic subgroups included: non-Hispanic white (NHW; 11,016, 65%), Hispanic (2,753, 16%), non-Hispanic black (NHB; 2,131, 13%), and Asian/Pacific Islander (API; 968, 6%) AYAs with HL. Across the full cohort, the 10-year and 15-year overall survival probabilities were 90% (95% confidence interval [95%CI]: 89 - 91) and 87% (95% CI: 86 - 88), respectively. At 10- and 15-years, overall survival was highest for NHWs (10-year: 92%: 15-year: 88%) and APIs (91%; 86%) compared to Hispanics (87%; 85%) and NHBs (82%; 78%). Overall survival, cause-specific survival, and percentage of deaths not attributed to HL by race/ethnicity are presented in the Figure. In the first year after diagnosis, 22% of deaths were due to causes other than primary disease, with the percentage of deaths not attributed to HL higher in NHWs and APIs than Hispanics and NHBs. At most time points after cancer diagnosis, a higher proportion of NHW (vs. NHB, Hispanic and API) patients died from causes other than HL. By 10 years after diagnosis, 25% of NHW patients died due to causes other than HL, vs. 20% in API, 17% in NHB, and 15% in Hispanic patients. By 15 years, 33% of all deaths were not attributed to HL. This was observed most dramatically in the NHW cohort in whom 40% of all deaths were not HL-related, compared to 24% of deaths in the NHB cohort and 26% - 27% of deaths in the Hispanic and API groups. Conclusion: In AYAs diagnosed with HL between 2000 and 2015, NHB patients had worse survival compared with NHW and API patients. The higher probability of survival in NHW patients was accompanied by a consistently higher proportion of non-cancer related death in this cohort both 10- years and 15-years after diagnosis. Studies are needed to evaluate risk factors for both short- and long-term mortality in AYAs, and to examine how these risks differ across racial/ethnic groups. Findings also suggest that despite increasing use of response-adapted therapy over the past two decades, all AYAs with HL remain at risk of death in the decades following therapy, further highlighting the need for long-term follow-up of this at-risk patient population. Figure. Figure. Disclosures Muffly: Adaptive Biotechnologies: Research Funding; Shire Pharmaceuticals: Research Funding.
6551 Background: During the past decade, a variety of initiatives have been implemented to improv... more 6551 Background: During the past decade, a variety of initiatives have been implemented to improve the accrual of cancer patients on clinical trials. In the U.S., these have included comprehensive reviews and recommendations by the two most recent National Cancer Institute (NCI) administrations, reorganization of the clinical trials infrastructure at the NCI, and campaigns by the NCI Cooperative Groups and their Coalition. During the past six years, additional funds were allocated to this effort as part of the doubling of the NCI budget. The impact of these efforts on national cancer treatment clinical trials was evaluated, with emphasis on age groups. Methods: Accrual data from NCI-sponsored treatment trials conducted between 1997 and 2006 were obtained from the NCI Cancer Therapy Evaluation Program. Entries were analyzed by patient age, gender, race, type of cancer treated, and calendar year of trial entry. Results: Overall, national cancer treatment trial entries declined after 9–11–2001 and in 2003 reached the lowest levels since 1997. As of 2005 accrual recovered to pre 9–11 levels only in 15–29 and &gt;60 year-olds, with the former demonstrating the greatest gain ( Table ). Entries among &lt;15 and 30–49 year- olds declined steadily since 1997 with no evidence for recovery as of 2005 ( Table ). Overall, the estimated proportion of the nation's cancer patients entered onto national treatment trials remains below 3%. Conclusions: Despite continued national and local efforts to increase the participation of cancer patients on clinical trials, accompanied by significant increases in the NIH and NCI budgets, there is little evidence of a beneficial impact. The effect of 9–11 has yet to be overcome, except in young and elderly adults, in whom specific, targeted initiatives appear to have been successful. The latter approaches may be useful to apply to other age groups, particularly in view of the recent cuts in the cooperative group budgets and current mandated decreases in study accruals. No significant financial relationships to disclose. [Table: see text]
18034 Background: In the U.S., children with ALL have had a dramatic mortality rate reduction whe... more 18034 Background: In the U.S., children with ALL have had a dramatic mortality rate reduction whereas older patients have not (Proc. ASCO 21: 389a, 2002), a difference that has been known since 2000 to be largely attributable to differences in pediatric versus adult treatment regimens (Blood 2000;96:467a,abstr; J Clin Oncol 2003;21:774–80; Leukemia 2004;18:2032–5; Pediat Blood Cancer 2005;45:578,Abstr; J Clin Oncol 2006;24(18S):#9024,abstr; Pediatr Blood Cancer 2006,43:748–56). To ascertain whether there has been any improvement in the U.S. since these reports, national mortality rates were assessed as a function of year of age and year of diagnosis. Methods: National ALL deaths and death rates during 1969–2004 were obtained from the U.S. SEER program (SEERStat, www.seer.cancer.gov accessed 1/8/08). Best fit regressions (linear, polynomial or exponential) were used to determine trends and estimate rates for specific calendar years. Results: Below age 15 the national ALL mortality rate has declined dramati...
7557 Background: Melanoma during the first three decades of life is rare, and small numbers of pa... more 7557 Background: Melanoma during the first three decades of life is rare, and small numbers of patients have precluded meaningful comparisons in children, adolescents and young adults. Methods: Using the SEER database, we investigated the incidence, clinical presentation, and outcome of melanoma in the first three decades of life. Results: The estimated incidence of melanoma in the year 2000 per million individuals increased with age and was projected to be projected to be 4.0 for 10–14yr olds (y/o), 15.5 for 15–19y/o, 44.4 for 20–24y/o, and 73.8 for 25–29y/o. Projecting prior trends to the year 2000, this equates to 114 new cases/yr among those < 15yr and 2586 cases/yr among those 15–29 yr. Melanoma accounted for < 3 % of all cancers in 0–14 yr olds, for 7.1% of all cancers in the 15–19yr age group, and for over 12% of all cancers in the 20–30-yr age group. From 1988–1999, the distribution of melanoma according to stage was as follows: < 20yr of age: in situ (n=99[number of cases];23%[% of total group]),...
Since the first edition of Cancer in Adolescents and Young Adults was published in 2007, there ha... more Since the first edition of Cancer in Adolescents and Young Adults was published in 2007, there have been numerous milestones in the journey of adolescent and young adult (AYA) oncology. These include an expansion of the age range from 15–29 to 15–39 years and a commensurate increase in the number and scope of the constituent chapters.
IMPORTANCE Previous studies have demonstrated that adolescents and young adults (AYAs) with cance... more IMPORTANCE Previous studies have demonstrated that adolescents and young adults (AYAs) with cancer are a distinct cancer population; however, research on long-term epidemiological trends and characteristics of cancers in AYAs is lacking. OBJECTIVE To characterize the epidemiology of cancer in AYAs aged 15 to 39 years with respect to (1) patient demographic characteristics, (2) frequencies of cancer types, and (3) cancer incidence trends over time. DESIGN, SETTING, AND PARTICIPANTS This retrospective, serial cross-sectional, populationbased study used registry data from the Surveillance, Epidemiology, and End Results (SEER) database from January 1, 1973, to December 31, 2015 (SEER 9 and SEER 18). The study population was from geographically distinct US regions, chosen to represent the racial and ethnic heterogeneity of the country. Initial analyses were performed from January 1 to August 31, 2019. MAIN OUTCOMES AND MEASURES Incidence rates and descriptive epidemiological statistics for patients aged 15 to 39 years with invasive cancer. RESULTS A total of 497 452 AYAs diagnosed from 1973 to 2015 were included in this study, with 293 848 (59.1%) female and 397 295 (79.9%) White participants. As AYAs aged, an increase in the relative incidence of carcinomas and decrease in the relative incidence of leukemias, lymphomas, germ cell and trophoblastic neoplasms, and neoplasms of the central nervous system occurred. Among the female AYAs, 72 564 (24.7%) were diagnosed with breast carcinoma; 48 865 (16.6%), thyroid carcinoma; and 33 828 (11.5%), cervix and uterus carcinoma. Among the male AYAs, 37 597 (18.5%) were diagnosed with testicular cancer; 20 850 (10.2%), melanoma; and 19 532 (9.6%), non-Hodgkin lymphoma. The rate of cancer in AYAs increased by 29.6% from 1973 to 2015, with a mean annual percentage change (APC) per 100 000 persons of 0.537 (95% CI, 0.426-0.648; P < .001). Kidney carcinoma increased at the greatest rate for both male (APC, 3.572; 95% CI, 3.049-4.097; P < .001) and female (APC, 3.632; 95% CI, 3.105-4.162; P < .001) AYAs. CONCLUSIONS AND RELEVANCE In this cross-sectional, US population-based study, cancer in AYAs was shown to have a unique epidemiological pattern and is a growing health concern, with many cancer subtypes having increased in incidence from 1973 to 2015. Continued research on AYA cancers is important to understanding and addressing the distinct health concerns of this population.
The efficacy of asparaginase in acute lymphoblastic leukemia (ALL) is dependent on depletion of a... more The efficacy of asparaginase in acute lymphoblastic leukemia (ALL) is dependent on depletion of asparagine, an essential amino acid for ALL cells. The target level of plasma asparaginase activity to achieve asparagine depletion has been between 0.05-0.4 IU/mL. COG AALL07P4 examined the asparaginase activity and plasma and CSF asparagine concentration of pegaspargase when given intravenously in the treatment of NCI high risk ALL. Matched plasma asparaginase/ asparagine levels of the clearance of 54 doses of pegaspargase given in induction or consolidation demonstrated that all patients who had a plasma asparaginase level >0.02 IU/mL had undetectable plasma asparagine. No difference was observed in CSF asparagine levels associated with matched plasma asparaginase levels of 0.02-0.05 vs. 0.05-0.22 IU/mL (p=0.25). Our data suggest that a plasma asparaginase activity level of 0.02 IU/mL can effectively deplete plasma asparagine. The data also indicate that the 95%CI for plasma asparagine depletion after a pegaspargase dose is 22-29 days.
Inclusion in cancer clinical trials is considered the optimal standard of care, offering improved... more Inclusion in cancer clinical trials is considered the optimal standard of care, offering improved patient experience and progressive survival gains for subsequent generations of patients. Adolescent and young adult (AYA) patients are underrepresented in cancer research; consequently, improvements in outcomes for AYAs lag behind their pediatric and adult counterparts. Despite international evidence of underrepresentation in research, systematically tested interventions to improve recruitment for AYAs do not exist, and recruitment rates for AYAs continue to be lower than those for children. We review recruitment of AYAs into trials and discuss barriers and facilitators.
This book, arranged in an MCQ format complemented by oral exam questions, is designed to meet the... more This book, arranged in an MCQ format complemented by oral exam questions, is designed to meet the needs of a wide range of examinees. Essential aspects of radiation physics, radiobiology, and clinical radiation oncology are well covered. Tumors at different sites are addressed in a series of individual chapters, and further chapters are devoted to lymphomas and total body irradiation, pediatric tumors, and rare tumors and benign diseases. The answer keys provide clear explanations for both the correct answers and incorrect statements.
Investigating the potential biological basis of age-related differences in outcome for AYA with c... more Investigating the potential biological basis of age-related differences in outcome for AYA with cancer could lead to a better understanding of the biology, facilitate the development of new diagnostic and predictive markers, and identify novel therapeutic targets and treatment approaches for AYA patients. The evidence that cancers in AYA patients may differ biologically from those in older and younger populations includes data from numerous laboratories. However, much of this evidence is preliminary, and large comprehensive studies to confirm and validate these findings are only now beginning to get underway. Indeed, there may be substantial differences in biological and molecular features between different age groups even within the population of AYA patients with a specific cancer type. If age is a good surrogate for a unique tumor biology associated with AYA cancers, then studies of cancers in AYA patients will almost certainly illuminate alternative tumorigenic pathways and will also likely benefit patients in other age groups whose tumors exhibit similar biological/molecular features. The biologic, molecular, and clinical features of five AYA cancers (colon, breast, acute lymphoblastic leukemia, melanoma, and sarcoma) are highlighted in this chapter, and the current state of research for each of them is examined. What will be required to better diagnose, treat, and predict response in patients with AYA cancer is also discussed.
While the epidemiology of cancer has been studied in children and older adults for more than a ha... more While the epidemiology of cancer has been studied in children and older adults for more than a half century, little attention had been paid to the cancers in between those that occur in the older adolescents and young adult (AYA) between 15 and 40 years of age. Yet as recently ascertained, more than a million new cases of invasive cancer are diagnosed in AYAs annually worldwide. Not only are the array of cancers that are diagnosed in AYAs unique, accumulating evidence suggests that many are biologically distinct from what appears to be the same neoplasm in younger and older persons. AYA cancers may thereby have different etiologies and require different therapeutic strategies. Many cancers peak in incidence in AYAs, and there is an intermediate peak between the well-known childhood cancer peak and the predominant one that occurs in the elderly. If the cancers that account for the childhood peak are embryonal/fetal cancers and those that account for the peak late in life as the cancers of aging, the AYA peak may be considered as due to cancers of intermediate growth and maturation. For most of the past quarter century, the incidence of the AYA cancers has been increasing for reasons that have not been ascertained. In Europe, the United States, and Japan, the 5-year survival rates of the vast majority of cancers in AYA have been remarkably similar. In the United States, the overall rate of survival improvement had been less in AYAs than in either younger or older patients. The trends and patterns of incidence do offer certain clues as to cancer causation in AYAs and potential methods of prevention. Detailed analyses of incidence patterns by geographic region and demographic factors together with determination of variations in incidence in time and space should provide additional insights into etiology and separate lines of investigation and therapeutic opportunities.
After a half century of clinical trials, expansive observations, vigorous advocacy and debate, sc... more After a half century of clinical trials, expansive observations, vigorous advocacy and debate, screening mammography could not be in a more controversial condition, especially the potential harm of overdiagnosis. Despite a simple rationale (catch the cancer early and either prevent death or at least decrease the amount of therapy needed for cure), the estimates to date of overdiagnosis rates are conflicting and the interpretations complex. Since the author&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s 2012 publication in the New England Journal of Medicine (NEJM), the peer-reviewed publications on overdiagnosis caused by screening mammography are reviewed and the NEJM analyses updated with three additional calendar years of results. The recent peer-reviewed medical literature on screening mammography induced overdiagnosis of breast cancer has increased exponentially, nearly 10-fold in 10 years. The average estimate of overdiagnosis is about 30%, but the range extends from 0% to 70+%. An update of the NEJM report estimates that in the US, 78,000 women and 30%-31% of those diagnosed with breast cancer at the age of 40 years or older during 2011 were overdiagnosed. Until we have better screening procedures that identify who really has cancer and needs to be treated, the risk of overdiagnosis relative to the benefit of screening merits more effective public and professional education. Radiologists, pathologists, and other professionals involved with screening mammography should recognize that the potential harm of overdiagnosis is downplayed or not discussed with the patient and family, despite agreement that the objective is informed choice.
Despite the increase in thyroid cancer incidence among adolescents and young adults (AYAs), this ... more Despite the increase in thyroid cancer incidence among adolescents and young adults (AYAs), this group has received limited attention. We reviewed the epidemiology and challenges of thyroid cancer care among AYAs, and proposed a research agenda to improve their care. Thyroid cancer is the most common cancer in American adults 16-33 years of age. AYAs with thyroid cancer face challenges including overdiagnosis reduced healthcare access and inconsistent care. Successful treatment of these patients results in additional challenges due to ongoing side effects of treatment as well as lasting impacts on their quality of life. These challenges should fuel a collaborative research agenda aimed at improving the quality of care for AYAs with thyroid cancer across the spectrum of diagnosis, treatment and survivorship.
Background: Hodgkin lymphoma (HL) is one of the most common, and one of the most curable cancers ... more Background: Hodgkin lymphoma (HL) is one of the most common, and one of the most curable cancers in adolescents and young adults (AYAs) (15-39 years). Despite excellent outcomes in the majority of patients, the burden of long-term morbidity and mortality persists. Prior analyses of patients treated for HL before the year 2000 have reported mortality rates as high as 30% by 20 years. Further, this mortality risk has historically differed across different racial and ethnic groups. Over the past decade, cooperative groups have expanded the use of risk-adapted, response-based treatment in an effort to maintain high cure rates, while simultaneously reducing the burden of late effects. We examined long-term survival in AYAs with HL treated after the year 2000. Methods: We used the National Cancer Institute Surveillance, Epidemiology, and End Results registry data for 18 regions in the United States (SEER18) to examine survival in AYAs with a confirmed diagnosis of HL between 2000 and 2015. We obtained overall and cause-specific survival estimates for each year after cancer diagnosis (up to 15 years) for each racial/ethnic group with corresponding 95% confidence intervals. From these yearly survival estimates, we calculated the percentage of deaths not attributed to HL at 10- and 15-years after cancer diagnosis. Results: The final analysis included 16,868 HL patients. Racial/ethnic subgroups included: non-Hispanic white (NHW; 11,016, 65%), Hispanic (2,753, 16%), non-Hispanic black (NHB; 2,131, 13%), and Asian/Pacific Islander (API; 968, 6%) AYAs with HL. Across the full cohort, the 10-year and 15-year overall survival probabilities were 90% (95% confidence interval [95%CI]: 89 - 91) and 87% (95% CI: 86 - 88), respectively. At 10- and 15-years, overall survival was highest for NHWs (10-year: 92%: 15-year: 88%) and APIs (91%; 86%) compared to Hispanics (87%; 85%) and NHBs (82%; 78%). Overall survival, cause-specific survival, and percentage of deaths not attributed to HL by race/ethnicity are presented in the Figure. In the first year after diagnosis, 22% of deaths were due to causes other than primary disease, with the percentage of deaths not attributed to HL higher in NHWs and APIs than Hispanics and NHBs. At most time points after cancer diagnosis, a higher proportion of NHW (vs. NHB, Hispanic and API) patients died from causes other than HL. By 10 years after diagnosis, 25% of NHW patients died due to causes other than HL, vs. 20% in API, 17% in NHB, and 15% in Hispanic patients. By 15 years, 33% of all deaths were not attributed to HL. This was observed most dramatically in the NHW cohort in whom 40% of all deaths were not HL-related, compared to 24% of deaths in the NHB cohort and 26% - 27% of deaths in the Hispanic and API groups. Conclusion: In AYAs diagnosed with HL between 2000 and 2015, NHB patients had worse survival compared with NHW and API patients. The higher probability of survival in NHW patients was accompanied by a consistently higher proportion of non-cancer related death in this cohort both 10- years and 15-years after diagnosis. Studies are needed to evaluate risk factors for both short- and long-term mortality in AYAs, and to examine how these risks differ across racial/ethnic groups. Findings also suggest that despite increasing use of response-adapted therapy over the past two decades, all AYAs with HL remain at risk of death in the decades following therapy, further highlighting the need for long-term follow-up of this at-risk patient population. Figure. Figure. Disclosures Muffly: Adaptive Biotechnologies: Research Funding; Shire Pharmaceuticals: Research Funding.
6551 Background: During the past decade, a variety of initiatives have been implemented to improv... more 6551 Background: During the past decade, a variety of initiatives have been implemented to improve the accrual of cancer patients on clinical trials. In the U.S., these have included comprehensive reviews and recommendations by the two most recent National Cancer Institute (NCI) administrations, reorganization of the clinical trials infrastructure at the NCI, and campaigns by the NCI Cooperative Groups and their Coalition. During the past six years, additional funds were allocated to this effort as part of the doubling of the NCI budget. The impact of these efforts on national cancer treatment clinical trials was evaluated, with emphasis on age groups. Methods: Accrual data from NCI-sponsored treatment trials conducted between 1997 and 2006 were obtained from the NCI Cancer Therapy Evaluation Program. Entries were analyzed by patient age, gender, race, type of cancer treated, and calendar year of trial entry. Results: Overall, national cancer treatment trial entries declined after 9–11–2001 and in 2003 reached the lowest levels since 1997. As of 2005 accrual recovered to pre 9–11 levels only in 15–29 and &gt;60 year-olds, with the former demonstrating the greatest gain ( Table ). Entries among &lt;15 and 30–49 year- olds declined steadily since 1997 with no evidence for recovery as of 2005 ( Table ). Overall, the estimated proportion of the nation's cancer patients entered onto national treatment trials remains below 3%. Conclusions: Despite continued national and local efforts to increase the participation of cancer patients on clinical trials, accompanied by significant increases in the NIH and NCI budgets, there is little evidence of a beneficial impact. The effect of 9–11 has yet to be overcome, except in young and elderly adults, in whom specific, targeted initiatives appear to have been successful. The latter approaches may be useful to apply to other age groups, particularly in view of the recent cuts in the cooperative group budgets and current mandated decreases in study accruals. No significant financial relationships to disclose. [Table: see text]
18034 Background: In the U.S., children with ALL have had a dramatic mortality rate reduction whe... more 18034 Background: In the U.S., children with ALL have had a dramatic mortality rate reduction whereas older patients have not (Proc. ASCO 21: 389a, 2002), a difference that has been known since 2000 to be largely attributable to differences in pediatric versus adult treatment regimens (Blood 2000;96:467a,abstr; J Clin Oncol 2003;21:774–80; Leukemia 2004;18:2032–5; Pediat Blood Cancer 2005;45:578,Abstr; J Clin Oncol 2006;24(18S):#9024,abstr; Pediatr Blood Cancer 2006,43:748–56). To ascertain whether there has been any improvement in the U.S. since these reports, national mortality rates were assessed as a function of year of age and year of diagnosis. Methods: National ALL deaths and death rates during 1969–2004 were obtained from the U.S. SEER program (SEERStat, www.seer.cancer.gov accessed 1/8/08). Best fit regressions (linear, polynomial or exponential) were used to determine trends and estimate rates for specific calendar years. Results: Below age 15 the national ALL mortality rate has declined dramati...
7557 Background: Melanoma during the first three decades of life is rare, and small numbers of pa... more 7557 Background: Melanoma during the first three decades of life is rare, and small numbers of patients have precluded meaningful comparisons in children, adolescents and young adults. Methods: Using the SEER database, we investigated the incidence, clinical presentation, and outcome of melanoma in the first three decades of life. Results: The estimated incidence of melanoma in the year 2000 per million individuals increased with age and was projected to be projected to be 4.0 for 10–14yr olds (y/o), 15.5 for 15–19y/o, 44.4 for 20–24y/o, and 73.8 for 25–29y/o. Projecting prior trends to the year 2000, this equates to 114 new cases/yr among those < 15yr and 2586 cases/yr among those 15–29 yr. Melanoma accounted for < 3 % of all cancers in 0–14 yr olds, for 7.1% of all cancers in the 15–19yr age group, and for over 12% of all cancers in the 20–30-yr age group. From 1988–1999, the distribution of melanoma according to stage was as follows: < 20yr of age: in situ (n=99[number of cases];23%[% of total group]),...
Since the first edition of Cancer in Adolescents and Young Adults was published in 2007, there ha... more Since the first edition of Cancer in Adolescents and Young Adults was published in 2007, there have been numerous milestones in the journey of adolescent and young adult (AYA) oncology. These include an expansion of the age range from 15–29 to 15–39 years and a commensurate increase in the number and scope of the constituent chapters.
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