Clinical and Translational Gastroenterology

 are the first to define specific geographic areas in the US where women diagnosed with colorectal cancer (CRC) before age 50 have higher mortality rates.

The results emphasize the importance of defining patterns of variance in early-onset CRC survival in order to understand the impact of community health behaviors on early-onset CRC outcomes.

“Colorectal cancer is becoming more common in young adults, and we don’t entirely understand the ‘why’ just yet. This rising burden among young adults stresses the importance for accurate and early diagnosis of these malignancies,” lead author Andreana Holowatyj, PhD, MSCI, assistant professor of Medicine and Cancer Biology at Vanderbilt University Medical Center and Vanderbilt-Ingram Cancer Center, said in a press release.

 “Primary care physicians and gastroenterologists around the country, and particularly in Nashville and other hot spot regions, should keep colorectal tumors in the differential diagnosis of young patients presenting with signs/symptoms of colorectal cancer.”

Geographic hot spots were derived using data obtained from the Centers for Disease Control and Prevention national mortality data. In addition, researchers identified women ages 15 to 49 years diagnosed with CRC from 1999 to 2016 in the National Institutes of Health/National Cancer Institute’s Surveillance, Epidemiology, and End Results program.

Ultimately, approximately 1 in every 16 contiguous US counties were identified as hot spots (191 of 3,108). Moreover, 52.9% of hot spot counties (n = 101) were located in the South.

Of 28,790 women with early-onset CRC, 13.7% of cases (n = 3,954) resided in hot spot counties. Non-Hispanic Black individuals comprised on average 19.3% of the population in hot spot counties.

Notably, physical inactivity and fertility were community health behaviors that modestly correlated with hot spot residence among women with early-onset CRC (r = 0.21 and r = 20.23, respectively; 

 < .01). Specifically, nearly one quarter of adults living in hot spot counties reported no physical activity during their leisure time. Further, about 5% of women in these counties had a live birth in the past year.

Together, individual/community-level features accounted for distinct variance patterns in early-onset CRC survival among women (hot spot counties: 33.8%; non-hot spot counties: 34.1%).

“Together, these findings may inform cancer prevention/intervention strategies tailored to young patients and may ultimately help to inform knowledge to reverse early-onset CRC incidence trends and improve patient outcomes,” the authors wrote. “Additional studies to examine early-onset CRC incidence patterns by hot spot classification among women will be helpful to discern whether disease incidence rates are higher in regions with disproportionately high early-onset CRC mortality.”

The hot spot geography identified in this study differs from a similar study published earlier this year by Holowatyj et al. that revealed hot spot counties for early-onset CRC mortality among both men and women. In the prior study that looked at variation in overall early-onset CRC mortality, 92% of hot spot counties were also revealed to be in the South. However, for hot spots specifically among women, almost half of these counties were in the Midwest and Northeast.

“In our study published earlier this year, Nashville is not an area of high mortality for both men and women diagnosed with early-onset colorectal cancer, but when you take a step back and look at only women, now Davidson County and Nashville emerge,” explained Holowatyj. “These results emphasize the need to understand these pronounced disparities in early-onset colorectal cancer burden not only by geographic region, but also by sex and race/ethnicity.”

Other large-population counties with high mortality rates for women diagnosed with early-onset CRC included Miami-Dade County, Cook County (Chicago), Fulton County (Atlanta), New Castle County (Wilmington, Del.), Fairfield County (Bridgeport, Conn.), St. Louis County, Bergen County (New Jersey suburbs of New York metropolitan area), Queens County (Queens borough of New York), Mecklenburg County (Charlotte, N.C.), Hamilton County (Cincinnati, Ohio), Tulsa County, and Philadelphia County.

1. Holowatyj AN, Langston ME, Han Y, et al. Community Health Behaviors and Geographic Variation in Early-Onset Colorectal Cancer Survival Among Women. 

2. Hot spots identified for colorectal cancer mortality rates among young women [news release]. Published November 19, 2020. Accessed November 20, 2020.

Articles

These results emphasize the importance of defining patterns of variance in early-onset CRC survival in order to understand the impact of community health behaviors on early-onset CRC outcomes. 

Study Defines Geographic Hot Spots of Early-Onset CRC Morality Among Women

A phase 2 nonrandomized clinical trial published in 

found that the combination of pembrolizumab (Keytruda) with bevacizumab (Avastin) and oral cyclophosphamide (Cytoxan) was well tolerated and demonstrated clinical benefit and durable treatment responses in patients with recurrent ovarian cancer.

Based on these study findings, researchers suggested that this combination may represent a future treatment strategy for this patient population.

“This clinical trial represents a significant conceptual advance in the use of combination therapy to enhance the efficacy of immunotherapy, demonstrating that we can generate long-term disease control in ovarian cancer without compromising quality of life,” senior author, Kunle Odunsi, MD, PhD, FRCOG, FACOG, deputy director, the Robert, Anne & Lew Wallace Endowed Chair in Cancer Immunotherapy, executive director of the Center for Immunotherapy, and the M. Steven Piver Professor of Gynecologic Oncology at Roswell Park Comprehensive Cancer Center, said in a press release.

 “The combination assessed in our trial is an option that should be considered for many patients with recurrent ovarian cancer based on its high tolerability and strong signal of efficacy.”

In this open-label, single-arm, cohort study, researchers enrolled patients with recurrent ovarian cancer, measurable disease per immune-related Response Evaluation Criteria in Solid Tumors (irRECIST), and an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 at a single institution in the US from September 6, 2016 to June 27, 2018. Participants received 200 mg pembrolizumab intravenously, 15 mg/kg bevacizumab every 3 weeks, and 50 mg oral cyclophosphamide once daily during the treatment cycle until disease progression, unacceptable toxic effects, or withdrawal of consent.

The dual primary end points were objective response rate (ORR) and progression-free survival (PFS).

“Pembrolizumab works by activating immune cells against cancer, but checkpoint inhibitors haven’t worked well in ovarian cancer because the T cells often can’t get to the tumor,” first author Emese Zsiros, MD, PhD, FACOG, a staff physician and faculty member with the department of Gynecologic Oncology and Center for Immunotherapy at Roswell Park, said in the release. “We combined bevacizumab, to normalize the tumor microenvironment and achieve better penetration of T cells into tumor tissue, and oral cyclophosphamide, which can deplete ‘bad’ regulatory T cells that actually help cancer cells to avoid immune attack, with checkpoint blockade in order to activate the ‘good’ killer T cells to fulfill their function.”

Among a total of 40 women enrolled in the trial, 30 (75.0%) had platinum-resistant and 10 (25.0%) had platinum-sensitive ovarian cancer with a mean (SD) age of 62.2 (9.4) years. The ORR was 47.5%. In total, 3 women (7.5%) had complete responses, 16 (40.0%) had partial responses, and 19 (47.5%) had stable disease in response to treatment based on irRECIST criteria.

Moreover, median PFS was 10.0 (90% CI, 6.5-17.4) months. Clinical benefit was also observed in 38 patients (95.0%) and durable responses were observed in 10 (25.0%).

Regarding safety, the most common grade 3 to 4 treatment-related adverse events (AEs) were hypertension (6 [15.0%]) and lymphopenia (3 [7.5%]). Further, the most frequently reported AEs included fatigue (18 [45.0%]), diarrhea (13 [32.5%]), and hypertension (11 [27.5%]).

“The quality of life of our patients who took part in this clinical trial was excellent,” Zsiros added. “Most of them were able to travel, spend good time with their families and resume their hobbies — cooking, hiking, things that they were not doing before. And approximately 30 percent of our patients were still living more than a year and a half after going on this combination, which we did not anticipate. These are very striking results.”

Of note though, an important limitation of the current study was its single-center, 1-arm design lacking a comparison arm to characterize the effect of each trial drug versus a dual regimen or traditional second-line therapy. Moving forward, these results are being followed up with further analysis of biospecimens to determine the synergistic mechanisms among immune checkpoint inhibitor, antiangiogenic therapy, and regulation T-cell depletion, thus allowing more patients to benefit from immunotherapy treatments in the future.

1. Zsiros E, Lynam S, Attwood KM, et al. Efficacy and Safety of Pembrolizumab in Combination With Bevacizumab and Oral Metronomic Cyclophosphamide in the Treatment of Recurrent Ovarian Cancer. 

2. Roswell Park Reports Positive Outcomes from New Combination Treatment for Ovarian Cancer [news release]. Buffalo, NY. Published November 19, 2020. Accessed November 20, 2020. https://www.roswellpark.org/newsroom/202011-roswell-park-reports-positive-outcomes-new-combination-treatment-ovarian-cancer?utm_source=Cision&utm_medium=Email&utm_term=Nov-20&utm_content=Immunotherapy%2c+chemotherapy%2c+Keytruda%2c+pembrolizumab%2c+ovarian%2c+cancer%2c+research

A phase 2 trial found that the combination of pembrolizumab with bevacizumab and oral cyclophosphamide was well tolerated and demonstrated clinical benefit and durable treatment responses in patients with recurrent ovarian cancer.

Phase 2 Trial Reports Positive Outcomes with Treatment Combination for Ovarian Cancer 

Results from the phase 3 BOSTON study, published in 

, suggested that a once-per-week combination regimen of selinexor (Xpovio), bortezomib (Velcade), and dexamethasone (Ozurdex) is a novel, effective, and convenient treatment option for patients with multiple myeloma who have received 1 to 3 previous lines of therapy.

"The results from the BOSTON study published in 

 demonstrate that the once-weekly regimen of [selinexor] and [bortezomib], with low-dose dexamethasone reduced the risk of disease progression or death by 30% and induced a higher rate of overall and deep responses compared to patients receiving a standard twice-weekly [bortezomib] and low-dose dexamethasone regimen,” co-senior author Paul Richardson, MD, clinical program leader and director of Clinical Research at the Jerome Lipper Multiple Myeloma Center at the Dana-Farber Cancer Institute, said in a press release.

 “This was observed despite approximately 40% less [bortezomib], 25% less dexamethasone, and approximately 35% fewer clinic visits on the [selinexor-bortezomib-dexamethasone] arm as compared with the standard [bortezomib-dexamethasone] therapy arm.”

“Encouragingly, the efficacy of the [selinexor-bortezomib-dexamethasone] regimen was consistent and noteworthy across several key subgroups, including patients who were frail or 65 years and older, patients with high-risk cytogenetics, patients with moderate renal impairment and patients who had either prior bortezomib or lenalidomide treatment,” Richardson added.

The BOSTON study was conducted at 123 sites in 21 countries and included 402 adult patients with relapsed or refractory multiple myeloma who had received 1 to 3 prior lines of therapy. Participants were randomly assigned 1:1 to receive either 100 mg selinexor once per week, 1.3 mg/m2 bortezomib once per week, and 20 mg dexamethasone twice per week, or 1.3 mg/m2 bortezomib twice per week for the first 24 weeks and once per week thereafter along with 20 mg dexamethasone 4 times per week for the first 24 weeks and twice per week thereafter.

Notably, the BOSTON study allowed for patients on the control arm to crossover to the selinexor-bortezomib-dexamethasone arm following objective progression of disease verified by an Independent Review Committee (IRC).

The primary end point of the study was progression-free survival (PFS) in the intention-to-treat population and key secondary end points included overall response rate (ORR) and rate of peripheral neuropathy, among others. Importantly, the trial is ongoing, with 55 patients remaining on randomized therapy as of February 20, 2020.

Overall, 195 patients (49%) were randomized to the selinexor, bortezomib, and dexamethasone group and 207 (51%) to the bortezomib and dexamethasone group and the first dose of study medication was given between June 6, 2017, and Feb 5, 2019. Median follow-up durations were 13.2 months (IQR 6.2-19.8) for the selinexor, bortezomib, and dexamethasone group and 16.5 months (9.4-19.8) for the bortezomib and dexamethasone group.

Median PFS was 13.93 months (95% CI, 11.73-not evaluable) with selinexor, bortezomib, and dexamethasone and 9.46 months (8.11-10.78) with bortezomib and dexamethasone (HR 0.70; 95% CI, 0.53.0.93; 

= .0075). Those in the selinexor, bortezomib, and dexamethasone arm also demonstrated a significantly greater ORR compared to the bortezomib and dexamethasone arm (76.4% vs. 62.3%, 

Moreover, patients who had received only one prior line of therapy demonstrated a higher ORR on the selinexor, bortezomib, and dexamethasone arm as compared to the bortezomib and dexamethasone arm (80.8% vs. 65.7%, 

= .0082). Importantly, selinexor, bortezomib, and dexamethasone therapy compared to standard bortezomib-dexamethasone therapy also showed consistent PFS benefit and higher ORR across several important subgroups.

Regarding safety, the most frequent grade 3 to 4 adverse events (AEs) were thrombocytopenia (77 [39%] of 195 patients in the selinexor, bortezomib, and dexamethasone group vs. 35 [17%] of 204 in the bortezomib and dexamethasone group), fatigue (26 [13%] vs 2 [1%]), anemia (31 [16%] vs 20 [10%]), and pneumonia (22 [11%] vs 22 [11%]). Further, peripheral neuropathy of grade 2 or above was less frequent with selinexor, bortezomib, and dexamethasone (41 [21%] patients) than with bortezomib and dexamethasone (70 [34%] patients; OR 0.50; 95% CI, 0.32-0.79; 

= .0013). Forty-seven (24%) patients in the selinexor, bortezomib, and dexamethasone group and 62 (30%) in the bortezomib and dexamethasone group died.

"We believe the successful outcome of this study represents an important advancement for myeloma patients and we are sincerely grateful to all of the patients and investigators who participated in the BOSTON study,” Sharon Shacham, PhD, MBA, president and chief scientific officer of Karyopharm, said in the release. “While [selinexor] received accelerated FDA approval last year for patients with penta-refractory multiple myeloma, a supplemental new drug application requesting approval for [selinexor] as a treatment for patients with multiple myeloma who have received one prior line of therapy has been accepted by the FDA and assigned a PDUFA action date of March 19, 2021. We are working closely with the regulatory authorities in both the US and Europe to make this potential new treatment option, with a completely novel mechanism of action, available to patients as quickly as possible, if approved."

1. Grosicki S, Simonova M, Spicka I, et al. Once-per-week selinexor, bortezomib, and dexamethasone versus twice-per-week bortezomib and dexamethasone in patients with multiple myeloma (BOSTON): a randomised, open-label, phase 3 trial. 

2. Karyopharm Announces Publication of XPOVIO® (Selinexor) Phase 3 BOSTON Study Results in The Lancet [news release]. Newton, Massachusetts. Published November 12, 2020. Accessed November 13, 2020. https://investors.karyopharm.com/2020-11-12-Karyopharm-Announces-Publication-of-XPOVIO-R-Selinexor-Phase-3-BOSTON-Study-Results-in-The-Lancet

The phase 3 BOSTON study suggested that a once-per-week combination regimen of selinexor (Xpovio), bortezomib (Velcade), and dexamethasone (Ozurdex) is an effective treatment option for patients with multiple myeloma who have received 1 to 3 previous lines of therapy.

Selinexor, Bortezomib, Dexamethasone Combination Effective for Patients with Multiple Myeloma

The first population-based study of lung cancer screening found that state-level screening rates were not aligned with disease burden, with the exception of Kentucky, which has supported comprehensive efforts to implement lung cancer screening.

“The increasing but low utilization of lung cancer screening reflects both ongoing efforts to screening eligible adults, and the many challenges to do so,” Stacey A. Fedewa, MPH, PhD, said in a press release.

 “Kentucky, which has supported screening implementation efforts, is unique as its screening rates are over twice the national average and four times that of other high lung cancer burden states like West Virginia and Arkansas.”

JNCI: The Journal of the National Cancer Institute

, indicates that deliberate efforts from various stakeholders are needed to boost lung cancer screening rates among eligible adults with a heavy smoking history, a group facing multiple barriers to lung cancer screening and cancer care.

To capture screening events, investigators utilized the American College of Radiology’s Lung Cancer Screening Registry (LCSR). Specifically, population-based surveys, US Census, and cancer registry data were used to estimate the number of eligible adults and lung cancer mortality.

Nationally, the screening rate was found to remain steady between 2016 (3.3%; 95% CI, 3.3%-3.7%) and 2017 (3.4%; 95% CI, 3.4%-3.9%), increasing to 5.0% (95% CI, 5.0-5.7) in 2018 (2018 vs 2016 screening rate ratio [SRR] = 1.52; 95%CI, 1.51-1.62).

“Medicare and most commercial insurers began covering [lung cancer screening] in 2015, likely contributing to increased utilization since reimbursement and cost is a frequently cited barrier among providers and patients,” the study authors noted. “We did not observe measurable increases until 2018, possibly due to the lag between insurance coverage and scaling up [lung cancer screening] in health systems.”

On the state level, in 2018 it was also found that several Southern states with a high lung-cancer burden, such as Mississippi, West Virginia, and Arkansas, had relatively low screening rates (<4%) among eligible adults, while several Northeastern states with a lower lung cancer burden, such as Massachusetts, Vermont, and New Hampshire, had the highest screening rates (12.5%-15.2%).

However, the exception to the above observations was Kentucky, which had the nation’s highest lung cancer mortality rate and one of the highest screening rates (13.7%).

Additionally, the study also found that compared to the national average, lung cancer screening rates were about 20% lower in states with a high proportion of uninsured adults who smoked and 40% lower in states with a relatively low number of lung cancer screening facilities. This suggests that there may be critical gaps in access to lung cancer screening.

According to sociodemographic factors, screening rates were positively correlated with the proportion of smokers who were female and negatively correlated with smokers who were Hispanic. Overall, the results showed that states with adults who smoked and are Hispanic had a significantly lower screening rate ratio than the national average.

“Even with a physician recommendation, [lung cancer screening] may be particularly hard to increase because of individual-level barriers, such as competing health and financial demands, unique values and beliefs among adults who smoke,” the authors explained. “Beliefs about screening may also vary by sociodemographic factors. Women may be more likely to benefit from screening and adhere to [lung cancer screening] guidelines.”

Importantly, this study was not without limitations, including that researchers assumed a uniform probability that a person was eligible for lung cancer screening given that they smoked cigarettes, recognizing that smoking duration and intensity may vary by state and the National Health Interview Survey estimate used in the study could be limited by small sample sizes. Moreover, the national number deemed eligible in the study approximated those of previous studies.

“Despite these limitations, our study has many strengths,” wrote the authors. “It provides the first population-based state-level screening data for all 50 states as well as a framework to do so as current state-based survey tools (i.e., [Behavioral Risk Factor Surveillance System]) do not ask questions on [low-dose computed tomography] in all states. These data are needed to inform state-level policy and lung cancer implementation efforts.”

1. Fedewa SA, Kazerooni EA, Studts JL, et al. State Variation in Low-Dose CT Scanning for Lung Cancer Screening in the United States. 

2. First Population-Based Study Finds State-Level Lung Cancer Screening Rates Not Aligned With Lung Cancer Burden in the U.S. [news release]. Published November 12, 2020. Accessed November 12, 2020. http://pressroom.cancer.org/LDCTScanLCS

This study found that state-level lung cancer screening rates were not aligned with disease burden, with the exception of Kentucky, which has supported comprehensive efforts to implement lung cancer screening.

State-Level Lung Cancer Screening Rates Do Not Align with Lung Cancer Burden

A multinational cohort study published in 

 suggested that experts have developed and validated a proposed American Joint Committee on Cancer (AJCC)-compliant clinical prognostic group staging system which can be used globally for patients with nonmetastatic prostate cancer and has better performance than the current AJCC 8th edition.

The new proposed system — called STAR-CAP — utilizes patient, tumor, and outcomes data from nearly 20,000 patients from 55 centers in the US, Canada, and Europe to create a robust model with strong prognostic power. According to the researchers, the high-quality evidence observed thus far supports the endorsement of this scoring system as a new staging system for prostate cancer.

“Localized prostate cancer is sometimes less aggressive, sometimes more — and whether we’re patients, physicians or researchers, we all want to know as best we can how aggressive a particular cancer is likely to be,” co-first author Robert Dess, MD, an assistant professor of radiation oncology at Michigan Medicine, said in a press release.

 “That information helps with our conversations with patients, it helps with clinical trial design and it is particularly valuable when you can make those estimates based off of standard information that you would collect when you first see a patient to discuss their treatment options.”

This study included 7 centers within the US, Canada, and Europe, 5 centers within the Shared Equal Access Regional Cancer Hospital (SEARCH) Veterans Affairs Medical Centers collaborative, and 43 centers within the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) registry. Patients included were those with cT1-4N0-1M0 prostate adenocarcinoma treated from January 1, 1992, to December 31, 2013.

The study cohort, dubbed the STAR-CAP cohort, was randomly divided into training and validation data sets. Importantly, statisticians were blinded to the validation data until the model was locked. A Surveillance, Epidemiology, and End Results (SEER) cohort was used as a second validation set.

Among a total of 19,684 patients included in the analysis (median age, 64.0 [IQR, 59.0-70.0] years), 12,421 were treated with radical prostatectomy and 7263 with radiotherapy. Median follow-up was 71.8 (IQR, 34.3-124.3) months; however, 4078 (20.7%) were followed up for at least 10 years.

The system assigns patients to a particular stage through a point system based on several variables, include age, tumor category, Gleason grade of cell abnormality, and prostate-specific antigen (PSA) levels. The model divides patients into 9 stages of non-metastatic prostate cancer based on their point score — from stage 1 to stage 3, with each stage split into substages of A, B and C.

In the validation set, predicted 10-year prostate cancer-specific mortality (PCSM) for the 9 score groups ranged from 0.3% to 40.0%. Notably, the 10-year C index (0.796; 95% CI, 0.760-0.828) exceeded that of the AJCC 8th edition (0.757; 95% CI, 0.719-0.792), revealing improvements across age, race, and treatment modality and within the SEER validation cohort. In addition, for a significant number of patients, the new model would reclassify them as having less advanced disease — for example, 22% of patients who would be classified as stage 3A under the AJCC’s 8th edition criteria would be classified as stage 1C using the STAR-CAP system, a downgrade of 4 classification steps.

“This is the kind of information that can give patients and doctors more confidence when discussing treatment options and expected outcomes,” said Dess.

Several years ago, the AJCC established criteria to evaluate prediction models for the staging of prostate cancer — however, since no models met the criteria, the most recent staging designations were based on the consensus of experts in the field.

“None of the previous models evaluated met the criteria, so none of them could be used,” co-senior author Daniel Spratt, MD, the Laurie Snow Endowed Research Professor of Radiation Oncology at Michigan Medicine, said in the release. “So, we said, ‘Well, let’s make one.’ We wanted it to be transparent, robust and validated, so that we can start moving closer to communicate using a common staging system, similar to other cancers. Right now, we primarily categorize people as low risk, intermediate risk or high risk — which is a fairly blunt and imprecise system.”

The scoring system is designed to be able to be used worldwide with information that is commonly gathered about a patient and their cancer. Importantly, this new system has been made available to doctors and researcher worldwide via a web-based app at 

“We know that some of the newest tools that we have that are just coming online like genomics or molecular imaging may improve upon this system, but we wanted to create the best, most widely accessible model based on the data we currently have — understanding that new tools may help us develop even better models in the future,” Dess explained.

1. Dess RT, Suresh K, Zelefsky MJ, et al. Development and Validation of a Clinical Prognostic Stage Group System. 

2. Toward a New Staging System for Prostate Cancer, and Why it Matters [news release]. Published October 22, 2020. Accessed November 19, 2020. https://www.newswise.com/articles/toward-a-new-staging-system-for-prostate-cancer-and-why-it-matters?sc=sphr&xy=10021790

According to the researchers, the high-quality evidence observed thus far supports the endorsement of this scoring system as a new staging system for prostate cancer.

STAR-CAP Suggested to be a Viable AJCC-Compliant Staging System for Prostate Cancer 

 suggested that adolescent and young adult (AYA) patients treated for acute myeloid leukemia (AML) have a high risk of developing long-term health complications.

The most common complications, or late effects as they are referred to in the study, observed among AYA survivors in this study were cardiovascular, endocrine, and respiratory diseases. Moreover, these complications were found to be more prevalent among non-white AYA patients and those living in more impoverished communities.

“Our study shed light on the high burden of late effects among young survivors of AML,” lead author Renata Abrahão, MD, MSc, PhD, a postdoctoral fellow at the UC Davis Comprehensive Cancer Center and the Center for Healthcare Policy and Research, said in a press release.

To estimate the cumulative incidence and investigate the main predictors of late effects among this patient population, researchers identified 1168 eligible AYAs with AML who survived at least 2 years after diagnosis from 1996 to 2012 in the California Cancer Registry. Importantly, late effects were reported from State hospital discharge data, and patients were followed through 2014.

Ultimately, the most common late effects reported at 10 years after diagnosis were endocrine (26.1%), cardiovascular (18.6%), and respiratory (6.6%), followed by neurologic (4.9%), liver/pancreatic (4.3%), renal (3.1%), avascular necrosis (2.7%), and second primary malignancies (2.4%). Moreover, of the total study cohort, 547 (46.8%) received a hematopoietic stem cell transplant (HSCT).

Following multivariable adjustments, the investigators found that AYAs who underwent HSCT or had non-favorable risk AML experienced an approximately 2-fold or higher increased likelihood of all late effects. Additionally, AYAs of Hispanic, Black, or Asian/Pacific Islander race or ethnicity and those who resided in lower socio-economic neighborhoods were shown to be at higher risk of numerous late effects when compared with non-Hispanic White patients.

“This higher risk may relate to the financial hardship that patients with cancer often experience,” senior author Theresa Keegan, PhD, MS, associate professor at the UC Davis Comprehensive Cancer Center, said in a press release. “As a result of cancer, AYA survivors and their families may miss work, experience income loss, and incur substantial out-of-pocket expenses.”

According to the researchers, many factors may have led to the observed disparities in disease burden. These include differences in therapeutic management, patient’s response to treatment, AML with high-risk mutations, coexisting diseases, and socioeconomic factors.

Further, compared to younger or older cancer survivors, the investigators indicated AYA patients suffer a higher financial burden. They may go without treatment and long-term follow-up visits that could mitigate the impact of late effects. Moreover, their risk of late effects may be exacerbated by unhealthy lifestyle habits such as smoking, excessive alcohol consumption, lack of exercise, non-protected sun exposure, and poor diet.

“Our findings underscore the need for long-term surveillance for the prevention, early detection and treatment of late effects, and can inform the development of AYA-focused consensus-based guidelines that will ultimately improve the quality of life and survival of these young vulnerable patients,” the study authors wrote.

1. Abrahão R, Huynh JC, Benjamin DJ, et al. Chronic medical conditions and late effects after acute myeloid leukaemia in adolescents and young adults: a population-based study. 

2. Young survivors of acute myeloid leukemia have long-term complications from treatment [news release]. Published November 9, 2020. Accessed November 17, 2020. https://www.newswise.com/articles/young-survivors-of-acute-myeloid-leukemia-have-long-term-complications-from-treatment?sc=sphr&xy=10019792

These results suggested that adolescent and young adult patients treated for acute myeloid leukemia have a high risk of developing long-term health complications.