5-year Survivors Research Articles

Risks of adverse obstetric outcomes among female survivors of adolescent and young adult cancer in England (TYACSS): a population-based, retrospective cohort study

There are limited data on the risks of obstetric complications among survivors of adolescent and young adult cancer with most previous studies only reporting risks for all types of cancers combined. The aim of this study was to quantify deficits in birth rates and risks of obstetric complications for female survivors of 17 specific types of adolescent and young adult cancer. The Teenage and Young Adult Cancer Survivor Study (TYACSS)-a retrospective, population-based cohort of 200 945 5-year survivors of cancer diagnosed at age 15-39 years from England and Wales-was linked to the English Hospital Episode Statistics (HES) database from April 1, 1997, to March 31, 2022. The cohort included 17 different types of adolescent and young adult cancers. We ascertained 27 specific obstetric complications through HES among 96 947 women in the TYACSS cohort. Observed and expected numbers for births and obstetric complications were compared between the study cohort and the general population of England to identify survivors of adolescent and young adult cancer at a heighted risk of birth deficits and obstetric complications relative to the general population. Between April 1, 1997, and March 31, 2022, 21 437 births were observed among 13 886 female survivors of adolescent and young adult cancer from England, which was lower than expected (observed-to-expected ratio: 0·68, 95% CI 0·67-0·69). Other survivors of genitourinary, cervical, and breast cancer had under 50% of expected births. Focusing on more common (observed ≥100) obstetric complications that were at least moderately in excess (observed-to-expected ratio ≥1·25), survivors of cervical cancer were at risk of malpresentation of fetus, obstructed labour, amniotic fluid and membranes disorders, premature rupture of membranes, preterm birth, placental disorders including placenta praevia, and antepartum haemorrhage. Survivors of leukaemia were at risk of preterm delivery, obstructed labour, postpartum haemorrhage, and retained placenta. Survivors of all other specific cancers had no more than two obstetric complications that exceeded an observed-to-expected ratio of 1·25 or greater. Survivors of cervical cancer and leukaemia are at risk of several serious obstetric complications; therefore, any pregnancy should be considered high-risk and would benefit from obstetrician-led antenatal care. Despite observing deficits in birth rates across all 17 different types of adolescent and young adult cancer, we provide reassurance for almost all survivors of adolescent and young adult cancer concerning their risk of almost all obstetric complications. Our results provide evidence for the development of clinical guidelines relating to counselling and surveillance of obstetrical risk for female survivors of adolescent and young adult cancer. Children with Cancer UK, The Brain Tumour Charity, and Academy of Medical Sciences.

Trends in allogeneic hematopoietic cell transplantation survival using population-based descriptive epidemiology method: analysis of national transplant registry data.

Prognosis for patients undergoing hematopoietic cell transplantation (HCT) has been improving. Short-term survival information, such as crude survival rates that consider deaths immediately after the transplantation, may not be sufficiently useful for assessing long-term survival. Using the data of the Japanese HCT registry, the net survival rate of patients who survived for a given period was determined according to age, disease, and type of transplant. We included a total of 41,716 patients who received their first allogeneic hematopoietic cell transplantation between 1991 and 2015. For each disease, age group, graft source subcategory, net survival was calculated using the Pohar-Perme method, and 5-year conditional net survival (CS) was calculated. Ten-year net survivals of total patient cohort were 41.5% and 47.4% for males and females, respectively. Except for myelodysplastic syndrome, multiple myeloma, and adult T-cell leukemia/lymphoma, 5-year CS for 5-year transplant survivors exceeded 90%. CS was especially high for aplastic anemia, of which was over 100% for children and younger adults receiving cord blood, suggesting that these patients have similar longevity to an equivalent group from the general population. These findings provide useful information for long-term survival, and can serve as benchmark for comparisons among registries, including other cancers.

QOL-14. EPILEPTIC SEIZURES, ANTI-SEIZURE MEDICATIONS, AND NEUROCOGNITION IN SURVIVORS OF PEDIATRIC BRAIN TUMORS

Abstract BACKGROUND Younger age at diagnosis and cranial radiation therapy are associated with neurocognitive late complications in survivors of pediatric brain tumors (PBT). Less is known about the association between neurocognition and epileptic seizures, with the latter affecting 27% of 5-year survivors. This study aimed to explore whether epileptic seizures exacerbate neurocognitive late complications beyond treatment and demographic factors. METHODS Fifty-nine survivors of PBT who had experienced at least one epileptic seizure, and a control group of survivors matched on sex, age at diagnosis, and cancer treatment, all diagnosed at Skåne University Hospital, were included in the study. Demographic and clinical variables, along with neurocognitive measures of verbal and non-verbal reasoning, cognitive processing speed, working memory, and cognitive flexibility were collected from medical records. Neuropsychological scores, assessed on average 3.68 years after diagnosis, were transformed into z-scores employing age-adjusted norms (m=0, sd=1). Generalized linear models, controlling for increased intracranial pressure at diagnosis and tumor localization, were used to analyze the association between epileptic seizures, cumulative use of anti-seizure medications (ASM), and neurocognition. RESULTS Experiencing any type of epileptic seizures was associated with reduced processing speed (β = -0.91z, p<0.01) and cognitive flexibility (β =-1.05z, p<0.01). Treatment with one ASM was associated with reduced cognitive processing speed (β =-0.81z, p=0.03), and treatment with two or more ASM was associated with lower scores on measures of non-verbal reasoning (β =-0.81z, p<0.01), working memory (β =-0.77z, p=0.01), processing speed (β=-1.26z, p<0.01), and flexibility (β =-1.54z, p<0.01). CONCLUSIONS Epileptic seizures and treatment with ASM were both associated with neurocognitive late complications. Optimal seizure management presents a potential modifiable factor for reducing cognitive burden in survivors of PBT.

Cardiac Dysfunction Among Breast Cancer Survivors: Role of Cardiotoxic Therapy and Cardiovascular Risk Factors.

Cardiac dysfunction is the leading cause of mortality among 10-year breast cancer survivors. Limited information regarding long-term risks of cardiac dysfunction after cardiotoxic therapy (anthracyclines, trastuzumab/pertuzumab, radiation) has precluded development of surveillance guidelines for the survivors. Patients with breast cancer who completed cardiotoxic therapy underwent echocardiographic screening every 2 years. New-onset cardiac dysfunction was defined as left ventricular ejection fraction (LVEF) <50% after cardiotoxic therapy initiation and included early- and late-onset cardiac dysfunction. We evaluated 2,808 echocardiograms in 829 breast cancer survivors; the median age at breast cancer diagnosis was 54.2 years (range, 20.3-86.3); the median follow-up was 8.6 years (1.8-39.8); 39.7% received anthracyclines, 16% received trastuzumab/pertuzumab, 6.2% received both anthracyclines and trastuzumab/pertuzumab, and 38.1% received radiation alone. The cumulative incidence of cardiac dysfunction increased from 1.8% at 2 years to 15.3% at 15 years from cardiotoxic therapy initiation. Multivariable Cox regression analysis identified the following risk factors: non-Hispanic Black race (hazard ratio [HR], 2.15 [95% CI], 1.37 to 3.38), cardiotoxic therapies (anthracyclines: HR, 2.35 [95% CI, 1.25 to 4.4]; anthracyclines and trastuzumab/pertuzumab: HR, 3.92 [95% CI, 1.74 to 8.85]; reference: left breast radiation alone), selective estrogen receptor modulators (HR, 2.0 [95% CI, 1.2 to 3.33]), and precancer hypertension (HR, 3.16 [95% CI, 1.63 to 6.1]). Late-onset cardiac dysfunction was most prevalent among anthracycline- and radiation-exposed patients; early-onset cardiac dysfunction was most prevalent among patients exposed to anthracyclines and trastuzumab/pertuzumab; equal prevalence of both early- and late-onset cardiac dysfunction was observed in trastuzumab-/pertuzumab-exposed patients. Adjusted longitudinal analyses revealed an annual decline in LVEF by 0.29% (P = .009) over 20 years from breast cancer diagnosis. These findings provide evidence to support echocardiographic surveillance for several years after cardiotoxic therapy and also suggest a need to examine the efficacy of management of cardiovascular risk factors to mitigate risk.

Patient reported symptoms after cancer diagnosis and the risk of short- and long-term severe mental health events among adolescents and young adults (AYA): A population-based study.

12019 Background: AYA with cancer are a vulnerable sub-population at risk of adverse mental health outcomes during and after cancer treatment. Tools to identify AYA at highest risk are required to guide screening and interventions. In a population-based cohort of AYA with cancer, we determined whether self-reported symptoms were associated with subsequent short- and long-term severe mental health events (SMHE). Methods: All Ontario, Canada AYA diagnosed with cancer aged 15-29 between 2010-2018 were identified and linked to healthcare databases, including one capturing self-reported Edmonton Symptom Assessment System (ESAS) scores at cancer-related visits. Scores for depression, anxiety, and poor well-being were categorized as not measured, mild (0-3), moderate (4-6), or severe (7-9). SMHE were defined as emergency room visits or hospitalizations for mental health reasons. First, we used Cox proportional hazard models to determine the association of ESAS scores (time-varying variable) with subsequent SMHE. Second, among 5-year survivors, we determined the association of maximum ESAS score within the first year of diagnosis with long-term SMHE (i.e. starting at 5 years from cancer diagnosis). All analyses were adjusted for patient and disease variables, including mental healthcare use prior to cancer diagnosis. Results: 5,435 AYA met inclusion criteria. Median age at cancer diagnosis was 25 years [interquartile range 22-27]. Hematologic cancers were most common (1,748; 32.2%). Symptom severity was associated with subsequent SMHE risk. For example, AYA reporting severe anxiety were at more than three-fold higher risk of SMHE compared to those reporting mild anxiety [adjusted hazard ratio (aHR) 3.6, 95th confidence interval (CI) 1.9-6.7; p &lt; 0.001]. Similar risk was seen among AYA reporting severe vs. mild depression (aHR 3.5, 1.7-7.3; p &lt; 0.001). Among 3,518 (64.7%) 5-year survivors, symptom severity also predicted long-term SMHE. For example, starting at 5 years post cancer diagnosis, the subsequent 3-year cumulative incidence of a SMHE among those who reported severe depression at any time during the first year post cancer diagnosis was 10.5% (95CI 6.9-15.9) compared to 2.4% (95CI 1.7-3.3) among those who only reported mild depression (aHR 3.0, 95CI 1.8-4.9; p &lt; 0.0001). Similar results were seen pertaining to severe anxiety and severe impact on well-being. AYA endorsing severe anxiety represented 13.1% of the cohort but accounted for 25.8% of AYA experiencing SMHEs during the first three years of survivorship. Conclusions: Systematic symptom screening in the first year after cancer diagnosis identifies a proportion of AYA at high risk of both short and long-term SMHE who may benefit from targeted screening and interventions. Future work will determine whether interventions during cancer treatment mitigate this risk.

Tamoxifen for breast cancer prevention among survivors of pediatric lymphoma previously treated with chest radiation: Clinical benefits, harms and tradeoffs.

10025 Background: Survivors of pediatric lymphoma previously treated with chest radiation are at high risk for subsequent breast cancer. Although early initiation of breast cancer screening is recommended, the clinical benefits and harms of adding tamoxifen to reduce breast cancer deaths among these women are unknown. Methods: We adapted a Cancer Intervention and Surveillance Modeling Network (CISNET) breast model using data from the Childhood Cancer Survivor Study (CCSS) to reflect the elevated risks for breast cancer and competing mortality for 5-year survivors previously treated with chest radiation (RT). Breast cancer risk was based on age, chest RT field, timing of RT relative to menarche, menopause status, anthracycline exposure, and family history. Premature menopause risk varied by cumulative ovarian RT and alkylator dose. Based on the US Preventive Services Task Force 2019 Evidence Summary, we assumed tamoxifen (20mg daily for 5 years) reduced estrogen receptor positive (ER+) breast cancer risk by 42% (RR = 0.58 [0.42-0.81]) for 20 years and increased risks for venous thromboembolism, deep vein thrombosis, coronary heart disease, stroke and endometrial cancer during treatment. Strategies included no screening or tamoxifen, annual screening with mammography and MRI starting at age 25, annual screening with mammography and MRI starting at age 25 with the addition of tamoxifen at ages 25, 30 or 35. Model outcomes included cumulative breast cancer risk, number of childbearing years before age 45 (defined as years menstruating without tamoxifen use or a breast cancer diagnosis or having survived breast cancer for at least 3 years), and number of tamoxifen-related side-effects. Results: Among a cohort of 20-year-old 5-year lymphoma survivors previously treated with mediastinal RT without primary ovarian failure, an estimated 20% were projected to develop breast cancer and 2.6% would die from the disease before age 50 in the absence of screening or tamoxifen use. Survivors would have on average 22 childbearing years before age 45. Early initiation of breast cancer screening at age 25 would reduce breast cancer deaths before age 50 by 56.3%. Depending on age at initiation, tamoxifen would further reduce breast cancer deaths by 8.0 to 9.6 percentage points for an overall 64.3% to 65.9% reduction and reduce the average number of childbearing years by 17% to 21%. For each breast cancer death averted, a reduction of 1950 to 3740 childbearing life years and 11 to 20 side-effects would occur and varied by the tamoxifen start age compared to mammography and MRI screening. Conclusions: Tamoxifen use for primary breast cancer prevention among pediatric lymphoma survivors may further reduce breast cancer deaths but decisions might depend on survivor preferences for side effects vs. avoiding breast cancer and consideration of timing for childbearing.

Aerobic exercise training combined with local strength exercise restores muscle blood flow and maximal aerobic capacity in long-term Hodgkin lymphoma survivors.

It is unclear whether muscle blood flow (MBF) is altered in long-term Hodgkin lymphoma (HL) survivors. We tested the hypothesis that 1) MBF response during mental stress (MS) is impaired in long-term HL survivors and 2) aerobic exercise training combined with local strength exercise (ET) restores MBF responses during MS in these survivors. Eighteen 5-year HL survivors and 10 aged-paired healthy subjects (HC) were studied. Twenty HL survivors were randomly divided into two groups: exercise-trained (HLT, n = 10) and untrained (HLUT, n = 10). Maximal aerobic capacity was evaluated by a cardiopulmonary exercise test and forearm blood flow (FBF) by venous occlusion plethysmography. MS was elicited by Stroop color and word test. ET was conducted for 4 mo, 3/wk for 60 min each session. The aerobic exercise intensity corresponded to anaerobic threshold up to 10% below the respiratory compensation point. The strength exercises consisted of two to three sets of chest press, pulley and squat exercises, 12-15 repetitions each exercise at 30-50% of the maximal voluntary contraction. Baseline was similar in HL survivors and HC, except peak oxygen consumption (peak V̇o2, P = 0.013) and FBF (P = 0.006) that were lower in the HL survivors. FBF responses during MS were lower in HL survivors (P < 0.001). ET increased peak V̇o2 (11.59 ± 3.07%, P = 0.002) and FBF at rest (33.74 ± 5.13%, P < 0.001) and during MS (24 ± 5.31%, P = 0.001). Further analysis showed correlation between the changes in peak V̇o2 and the changes in FBF during MS (r = 0.711, P = 0.001). In conclusion, long-term HL survivors have impaired MBF responses during MS. ET restores MBF responses during MS.NEW & NOTEWORTHY Long-term Hodgkin lymphoma (HL) survivors have impaired muscle blood flow responses during mental stress and decreased maximal aerobic capacity. Supervised aerobic exercise training combined with local strength exercises restores muscle blood flow responses during mental stress and maximal aerobic capacity in these survivors. These findings provide evidence of safety and effectiveness of exercise training in HL survivors. Moreover, they highlight the importance of exercise training in the treatment of this set of patients.

Personalized risk assessment of new onset depression in long-term cancer survivors.

e13798 Background: Advances in cancer detection and treatment have improved long-term survival. It is critical to understand the impact that experiencing cancer has on psychological health, given that the prevalence of depression in long-term survivors is higher than in the general population. Our aim was to develop a risk prediction model to identify long-term (5-year) survivors at high risk of developing depression. Methods: We conducted a retrospective study of the SEER-Medicare database beneficiaries with localized breast, prostate, colon, or rectal cancer diagnosed between 2003-2011 who had survived at least 5 years since diagnosis. We required Part D coverage in the breast cohort to account for adjuvant endocrine therapy. Our primary outcome was the cumulative incidence of depression between 5-10 years after diagnosis, which was defined using a claims-based algorithm as a single or recurrent episode of major depressive disorder, recent episode of bipolar I disorder, or dysthymic disorder. For each cancer site, we constructed restricted mean survival time models, a non-parametric method that yields time ratios; a time ratio (TR) &lt; 1 indicates shorter mean time to event (TTE). Results: Our cohort consisted of 80,579 survivors. The cumulative incidence of depression occurring between 5-10 years after diagnosis was 16.9% for breast cancer, 7.8% for prostate cancer, 10.6% for colon cancer, and 8.6% for rectal cancer. The cumulative incidence of new onset depression increased over time and was 7.2% vs. 13.9% among survivors diagnosed before and after 2008, respectively. Compared with patients age &lt; 70 at diagnosis, patients aged 75 and older exhibited 5-10% shorter mean TTE across breast, prostate, and colon cancer. There was no association between Non-Hispanic (NH) Black race or Hispanic ethnicity and depression compared with NH White survivors. Asian survivors were at lower risk of developing depression. Disease specific factors, including stage, grade, hormone receptor status (breast), or PSA (prostate), did not predict depression in long-term survivors. Receipt of treatment in the 3-5 years after initial diagnosis was associated with moderately greater risk for all survivors, with the shortest mean TTE among breast cancer survivors (TR=0.91, 95% CI=0.85-0.97). Across all cohorts, the greatest predictor of depression was a prior history of depression. The incidence of depression in long-term survivors was 42% in patients with a prior history of depression vs. 8% among survivors without a prior history of depression. Conclusions: Diagnoses of depression increased in cancer patients since 2008 and were associated with prior history of depression, advanced age, census tract poverty, and continued treatment 3 years after diagnosis. Treatment type and disease specific factors were not strong predictors of depression.

Late mortality and chronic health conditions in long-term survivors of nasopharyngeal cancers: The 20-year follow-up of territory-wide Hong Kong Nasopharyngeal Cancer Survivor Study (HKNPCSS).

12045 Background: The survival rate of patients with nasopharyngeal cancer (NPC) has significantly improved in the last decade. However, there are only a few studies that have quantified the long-term morbidity and mortality that follow NPC treatment. This study aims to analyze the chronic health conditions, all-cause mortality, and cause-specific mortality among NPC survivors. Methods: The Hong Kong NPC Survivor Study (HKNPCSS) is a retrospective cohort study conducted across all six oncology centers in Hong Kong. It included longitudinal follow-up of 5-year survivors diagnosed with NPC between 1997 to 2015. We compared the standardized mortality ratio (SMRs) of 7893 survivors to a matched population in terms of age, sex, and calendar year. We also calculated the frequencies of chronic conditions of 7893 survivors and 23679 healthy individuals with matched age, sex, and date of cohort entry. Chronic health conditions were classified using the Common Terminology Criteria for Adverse Events. Cox proportional hazard models were used to estimate hazard ratios (HRs) for chronic health conditions. Results: The mean age of NPC survivors was 49.1 years, while healthy individuals had a mean age of 50.5 years. Among the 7893 NPC survivors, the 20-year cumulative all-cause mortality was 34.0% (95% CI, 29.1%-38.9%), with 1668 (59.9%) of 2785 deaths attributed to health-related causes. The SMR for NPC survivors compared to the general population was 3.81 (95% CI, 3.67-3.95), with the highest SMRs observed for pulmonary (SMR: 6.18, 95% CI, 5.73-6.64) and cardiovascular (SMR: 2.12, 95% CI, 1.90-2.36) causes. Among the survivors, 59.2% (n=4674) had severe, life-threatening, or fatal (grade 3-5) health conditions, with a 20-year cumulative incidence of 59.0% (95% CI, 56.4%-61.5%). The adjusted hazard ratio (HR) of grade 3-5 chronic condition in NPC survivors, compared to healthy cohorts, was 7.02 (95% CI, 6.64-7.42). Gastrointestinal (HR: 20.7), hearing, visual, and nasal (HR: 15.4), and neurological (HR: 8.39) conditions had the highest risks. Intensity modulated radiotherapy (IMRT), compared to non-IMRT, was associated with reduced risks of all-cause mortality (HR: 0.83, 95% CI, 0.74-0.91) and a trend towards reduced grade 3-5 chronic health conditions (HR: 0.89, 95% CI, 0.75-1.05). Conclusions: Even 20 years after diagnosis, NPC survivors still face increased risks of late mortality and morbidity. The findings emphasize the need for a comprehensive survivorship program to improve outcomes for NPC survivors.

The burden of cardiovascular disease and risk for subsequent major adverse cardiovascular events in survivors of childhood cancer: a prospective, longitudinal analysis from the St Jude Lifetime Cohort Study

The effect of the increasing lifetime burden of non-major cardiovascular conditions on risk for a subsequent major adverse cardiovascular event among survivors of childhood cancer has not been assessed. We aimed to characterise the prevalence of major adverse cardiovascular events and their association with the cumulative burden of non-major adverse cardiovascular events in childhood cancer survivors. This is a longitudinal cohort study with participant data obtained from an ongoing cohort study at St Jude Children's Research Hospital: the St Jude Lifetime Cohort Study (SJLIFE). Prospective clinical follow-up was of 5-year survivors of childhood cancer who were diagnosed when aged younger than 25 years from 1962 to 2012. Age-frequency, sex-frequency, and race-frequency matched community-control participants completed a similar one-time clinical assessment. 22 cardiovascular events were graded using a St Jude Children's Research Hospital-modified version of the National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.03). Cumulative incidence and burden of the primary outcome of major adverse cardiovascular events (cardiomyopathy, myocardial infarction, stroke, and other cardiovascular-related mortality) were estimated. Rate ratios (RR) of the association of major adverse cardiovascular events with 22 non-major adverse cardiovascular events were estimated using multivariable piecewise-exponential regression adjusting for attained age, age at diagnosis, sex, race and ethnicity, treatment era, diagnosis of diabetes, and exposure to cardiotoxic cancer therapies. The St Jude Lifetime Cohort study is registered with ClinicalTrials.gov, NCT00760656, and is ongoing. 9602 5-year survivors of childhood cancer, and 737 community controls were included in the longitudinal follow-up (from Sept 13, 2007, to Dec 17, 2021). The median follow-up was 20·3 years (IQR 12·0-31·4) from the date of primary cancer diagnosis (4311 [44.9%] were females). By the age of 50 years (analysis stopped at age 50 years due to the low number of participants older than that age), the cumulative incidence of major adverse cardiovascular events among survivors was 17·7% (95% CI 15·9-19·5) compared with 0·9% (0·0-2·1) in the community controls. The cumulative burden of major adverse cardiovascular events in survivors was 0·26 (95% CI 0·23-0·29) events per survivor compared with 0·009 (0·000-0·021) events per community control participant. Increasing cumulative burden of grade 1-4 non-major adverse cardiovascular events was associated with an increased future risk of major adverse cardiovascular events (one condition: RR 4·3, 95% CI 3·1-6·0; p<0·0001; two conditions: 6·6, 4·6-9·5; p<0·0001; and three conditions: 7·7, 5·1-11·4; p<0·0001). Increased risk for major adverse cardiovascular events was observed with specific subclinical conditions (eg, grade 1 arrhythmias [RR 1·5, 95% CI 1·2-2·0; p=0·0017]), grade 2 left ventricular systolic dysfunction (2·2, 1·6-3·1; p<0·0001), grade 2 valvular disorders (2·2, 1·2-4·0; p=0·013), but not grade 1 hypercholesterolaemia, grade 1-2 hypertriglyceridaemia, or grade 1-2 vascular stenosis. Among an ageing cohort of survivors of childhood cancer, the accumulation of non-major adverse cardiovascular events, including subclinical conditions, increased the risk of major adverse cardiovascular events and should be the focus of interventions for early detection and prevention of major adverse cardiovascular events. The US National Cancer Institute and the American Lebanese Syrian Associated Charities.

Fewer Feedback Opportunities and Health Perception of Gastric Cancer Survivors: Opportunities for Patient Education.

This study aimed to estimate the impact of having fewer opportunities for patient education on health perception of gastric cancer survivors by examining quality-of-life (QoL) responses from patients who had been away for chemotherapy for a year. The full-surveillance (FullSV) group was comprised of gastric cancer survivors with stage I cancer who completed preoperative and postoperative 3-, 6-, 9-, and 12-month surveillances. The returning (RTN) group was comprised of 1-year survivors of stage II cancer who had been away for chemotherapy for a year. Surveillance periods were utilized to provide patient education about expected postoperative weight changes. The European Organisation for Research and Treatment of Cancer QoL questionnaires were used to assess QoL. The study included a total of 278 patients (243 in the FullSV group and 35 in the RTN group). The baseline QoL was not significantly different between the groups. Significant differences in postoperative QoL were revealed by some scales (global health status/QoL, physical functioning, fatigue, financial difficulties, anxiety, dry mouth, and body image), all in favor of the FullSV group. Despite no significant difference in their actual weight changes, stronger weight dissatisfaction was revealed among the RTN group. Patients with fewer educational inputs for postoperative adjustment of weight perception were the ones with stronger dissatisfaction about current weight. The health perception of cancer survivors is under the constant influence of clinician feedback during patient education. For the best cancer survivorship care, sufficient opportunities for adjustment of health perception through patient education need to be ensured.

Clinical Outcomes and Quality of Life Measures Among 5-Year Survivors of Fenestrated-Branched Endovascular Aortic Repair in a Prospective Nonrandomized Study

Clinical Outcomes and Quality of Life Measures Among 5-Year Survivors of Fenestrated-Branched Endovascular Aortic Repair in a Prospective Nonrandomized Study

Chronic Health Conditions and Longitudinal Employment in Survivors of Childhood Cancer

Employment is an important factor in quality of life and provides social and economic support. Longitudinal data on employment and associations with chronic health conditions for adult survivors of childhood cancer are lacking. To evaluate longitudinal trends in employment among survivors of childhood cancer. Retrospective cohort study of 5-year cancer survivors diagnosed at age 20 years or younger between 1970 and 1986 enrolled in the multi-institutional Childhood Cancer Survivor Study (CCSS). Sex-stratified employment status at baseline (2002 to 2004) and follow-up (2014 to 2016) was compared with general population rates from the Behavioral Risk Factor Surveillance System cohort. Data were analyzed from July 2021 to June 2022. Cancer therapy and preexisting and newly developed chronic health conditions. Standardized prevalence ratios of employment (full-time or part-time, health-related unemployment, unemployed, not in labor force) among adult (aged ≥25 years) survivors between baseline and follow-up compared with the general population. Longitudinal assessment of negative employment transitions (full-time to part-time or unemployed at follow-up). Female participants (3076 participants at baseline; 2852 at follow-up) were a median (range) age of 33 (25-53) years at baseline and 42 (27-65) years at follow-up; male participants (3196 participants at baseline; 2557 at follow-up) were 33 (25-54) and 43 (28-64) years, respectively. The prevalence of full-time or part-time employment at baseline and follow-up was 2215 of 3076 (71.3%) and 1933 of 2852 (64.8%) for female participants and 2753 of 3196 (85.3%) and 2079 of 2557 (77.3%) for male participants, respectively, with declining standardized prevalence ratios over time (female participant baseline, 1.01; 95% CI, 0.98-1.03; follow-up, 0.94; 95% CI, 0.90-0.98; P < .001; male participant baseline, 0.96; 95% CI, 0.94-0.97; follow-up, 0.92; 95% CI, 0.89-0.95; P = .02). While the prevalence of health-related unemployment increased (female participants, 11.6% to 17.2%; male participants, 8.1% to 17.1%), the standardized prevalence ratio remained higher than the general population and declined over time (female participant baseline, 3.78; 95% CI, 3.37-4.23; follow-up, 2.23; 95% CI, 1.97-2.51; P < .001; male participant baseline, 3.12; 95% CI, 2.71-3.60; follow-up, 2.61; 95% CI, 2.24-3.03; P = .002). Among survivors employed full-time at baseline (1488 female participants; 1933 male participants), 285 female participants (19.2%) and 248 male participants (12.8%) experienced a negative employment transition (median [range] follow-up, 11.5 [9.4-13.8] years). Higher numbers and grades of chronic health conditions were significantly associated with these transitions. In this retrospective analysis of adult survivors of childhood cancer, significant declines in employment and increases in health-related unemployment among cancer survivors compared with the general population were identified. A substantial portion of survivors in the midcareer age range fell out of the workforce. Awareness among clinicians, caregivers, and employers may facilitate clinical counseling and occupational provisions for supportive work accommodations.

Risk of Subsequent Primary Cancers Among Adult-Onset 5-Year Cancer Survivors in South Korea: Retrospective Cohort Study.

The number of cancer survivors who develop subsequent primary cancers (SPCs) is expected to increase. We evaluated the overall and cancer type-specific risks of SPCs among adult-onset cancer survivors by first primary cancer (FPC) types considering sex and age. We conducted a retrospective cohort study using the Health Insurance Review and Assessment database of South Korea including 5-year cancer survivors diagnosed with an FPC in 2009 to 2010 and followed them until December 31, 2019. We measured the SPC incidence per 10,000 person-years and the standardized incidence ratio (SIR) compared with the incidence expected in the general population. Among 266,241 survivors (mean age at FPC: 55.7 years; 149,352/266,241, 56.1% women), 7348 SPCs occurred during 1,003,008 person-years of follow-up (median 4.3 years), representing a 26% lower risk of developing SPCs (SIR 0.74, 95% CI 0.72-0.76). Overall, men with 14 of the 20 FPC types had a significantly lower risk of developing any SPCs; women with 7 of the 21 FPC types had a significantly lower risk of developing any SPCs. The risk of developing any SPC type differed by age; the risk was 28% higher in young (<40 years) cancer survivors (SIR 1.28, 95% CI 1.16-1.42; incidence: 30 per 10,000 person-years) and 27% lower in middle-aged and older (≥40 years) cancer survivors (SIR 0.73, 95% CI 0.71-0.74; incidence: 80 per 10,000 person-years) compared with the age-corresponding general population. The most common types of FPCs were mainly observed as SPCs in cancer survivors, with lung (21.6%) and prostate (15.2%) cancers in men and breast (18.9%) and lung (12.2%) cancers in women. The risks of brain cancer in colorectal cancer survivors, lung cancer in laryngeal cancer survivors, and both kidney cancer and leukemia in thyroid cancer survivors were significantly higher for both sexes. Other high-risk SPCs varied by FPC type and sex. Strong positive associations among smoking-related cancers, such as laryngeal, head and neck, lung, and esophageal cancers, were observed. Substantial variation existed in the associations between specific types of FPC and specific types of SPC risk, which may be linked to hereditary cancer syndrome: for women, the risks of ovarian cancer for breast cancer survivors and uterus cancers for colorectal cancer survivors, and for men, the risk of pancreas cancer for kidney cancer survivors. The varying risk for SPCs by age, sex, and FPC types in cancer survivors implies the necessity for tailored prevention and screening programs targeting cancer survivors. Lifestyle modifications, such as smoking cessation, are essential to reduce the risk of SPCs in cancer survivors. In addition, genetic testing, along with proactive cancer screening and prevention strategies, should be implemented for young cancer survivors because of their elevated risk of developing SPCs.

Abstract PO2-12-02: Frailty among long-term breast cancer survivors

Abstract Background Cancer and its associated treatments may accelerate aging, resulting in increased frailty in survivors. However, the effect of breast cancer (BC) and treatment on frailty among long-term BC survivors has not been well investigated. This study aims to evaluate frailty prevalence and its association with clinical characteristics and treatment among 5-year BC survivors. Methods This study included 353 5-year BC survivors and 214 non-cancer control women aged ≥40 who were recruited to an ongoing breast health study at Vanderbilt University Medical Center between 2004 and 2017, and completed an online survey between May, 2022 and June 2023. Information collected includes demographics, lifestyle, disease history, and current health/functional status. A 26-item cumulative deficit index (CDI) was calculated as the proportion of deficits presented, including aging-related diseases, physical and mental health, activities of daily living, and social well-being, based on survey responses. CDI was categorized as robust (≤0.2), pre-frail (0.2-≤0.35), and frail ( &amp;gt;0.35). Cancer characteristics and treatment information was gathered from tumor registry. Multinomial logistic regression models were used to assess the association of CDI levels with case-control status, and BC clinical characteristics and cancer treatment among BC cases, with adjustment for age at survey (years), follow-up duration (5-≤10 and &amp;gt;10 years), and baseline Charlson comorbidity index (0, 1, and ≥2), and additional adjustment for BC stage and subtype in the analysis of treatment. Results The median time interval from BC diagnosis to survey was 12 years (range 5-34 years) for BC survivors. 90% of the participants were White. On average, BC patients were 3.8 years older at survey than controls [mean±SD (range) 64.5±9.2 (40-88) vs 60.7±10.3 (40-87), p&amp;lt; 0.001]. Among BC survivors, 41% had stage I, 39% stage II, and 8% stage III-IV cancer; 62% had a hormone receptor+/HER2- BC, followed by 22% HER2+ and 16% triple-negative BC. The majority of BC survivors underwent surgical resection (97%), and &amp;gt;50% received hormone therapy (59%), radiation therapy (53%), and chemotherapy (51%). BC survivors had a higher CDI score than controls (median 0.23 vs 0.19, p=0.01), with 34% and 18% of BC survivors being pre-frail and frail, compared with 25% and 16% in controls. After multivariable adjustment, BC survivors had a non-significantly increased prevalence of pre-frailty with odds ratio (OR) and 95% confidence interval (CI) of 1.49 (0.98-2.25), but a similar prevalence of frailty [OR (95% CI) = 1.08 (0.65-1.79)] compared to controls. BC survivors aged 40-65 had significantly elevated odds of pre-frailty [OR (95% CI) = 2.59 (1.44-4.63)]. Among BC survivors, frailty was significantly associated with stage [stage III-IV vs I: OR (95% CI) = 4.03 (1.27-12.78)] and chemotherapy [OR (95% CI) = 4.39 (1.71-11.30)], particularly among survivors aged ≥65 and 10-year survivors, but not BC subtype. Radiation therapy was associated with increased odds of pre-frailty among BC survivors aged 40-65. Conclusions This study suggests that long-term BC survivors younger than 65 are at increased odds of pre-frailty than non-cancer women. Frailty is associated with BC stage and chemotherapy among BC survivors, and radiotherapy among survivors younger than 65. More research is needed to investigate whether specific cancer treatment regimen is associated with frailty and other factors (e.g. lifestyle and genetics) that may modify the risk of frailty. The associations of frailty with cancer characteristics and treatments among breast cancer survivors Citation Format: Cong Wang, Jill De Vis, Kirsten Nguyen, Mason Alford, Brigitte Jia, Bapsi Chakravarthy, Xiao-Ou Shu. Frailty among long-term breast cancer survivors [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-12-02.

Sex-specific cardiovascular remodeling leads to a divergent sex-dependent development of heart failure in aged hypertensive rats

IntroductionThe prevalence of heart failure with preserved ejection fraction (HFpEF) is continuously rising and predominantly affects older women often hypertensive and/or obese or diabetic. Indeed, there is evidence on sex differences in the development of HF. Hence, we studied cardiovascular performance dependent on sex and age as well as pathomechanisms on a cellular and molecular level.MethodsWe studied 15-week- and 1-year-old female and male hypertensive transgenic rats carrying the mouse Ren-2 renin gene (TG) and compared them to wild-type (WT) controls at the same age. We tracked blood pressure and cardiac function via echocardiography. After sacrificing the 1-year survivors we studied vascular smooth muscle and endothelial function. Isolated single skinned cardiomyocytes were used to determine passive stiffness and Ca2+-dependent force. In addition, Western blots were applied to analyse the phosphorylation status of sarcomeric regulatory proteins, titin and of protein kinases AMPK, PKG, CaMKII as well as their expression. Protein kinase activity assays were used to measure activities of CaMKII, PKG and angiotensin-converting enzyme (ACE).ResultsTG male rats showed significantly higher mortality at 1 year than females or WT male rats. Left ventricular (LV) ejection fraction was specifically reduced in male, but not in female TG rats, while LV diastolic dysfunction was evident in both TG sexes, but LV hypertrophy, increased LV ACE activity, and reduced AMPK activity as evident from AMPK hypophosphorylation were specific to male rats. Sex differences were also observed in vascular and cardiomyocyte function showing different response to acetylcholine and Ca2+-sensitivity of force production, respectively cardiomyocyte functional changes were associated with altered phosphorylation states of cardiac myosin binding protein C and cardiac troponin I phosphorylation in TG males only. Cardiomyocyte passive stiffness was increased in TG animals. On a molecular level titin phosphorylation pattern was altered, though alterations were sex-specific. Thus, also the reduction of PKG expression and activity was more pronounced in TG females. However, cardiomyocyte passive stiffness was restored by PKG and CaMKII treatments in both TG sexes.ConclusionHere we demonstrated divergent sex-specific cardiovascular adaptation to the over-activation of the renin-angiotensin system in the rat. Higher mortality of male TG rats in contrast to female TG rats was observed as well as reduced LV systolic function, whereas females mainly developed HFpEF. Though both sexes developed increased myocardial stiffness to which an impaired titin function contributes to a sex-specific molecular mechanism. The functional derangements of titin are due to a sex-specific divergent regulation of PKG and CaMKII systems.

Cardiovascular screening outcomes in the Dutch survivorship care program for Hodgkin lymphoma survivors.

Hodgkin lymphoma (HL) survivors are at increased risk of cardiovascular disease (CVD) due to former lymphoma treatment. In 2013, cardiovascular screening for 5-year HL survivors according to national guidelines was implemented in Dutch survivorship clinics. We aim to assess the following: (1) adherence to screening guidelines and (2) the yield of (risk factors for) CVD in the screening program. The study population consisted of 5-year HL survivors who received survivorship care at three University Medical Centers from 2013 to 2016 through 2021. Patient characteristics, cardiovascular screening procedures, and outcomes were collected from the medical records. In 186 survivors eligible for cardiovascular screening (mean age 47.8years, 60.8% female), the following diagnostics were performed: complete blood tests (81.0%, median frequency: yearly instead of advised 5-yearly evaluation), electrocardiogram (93.0%), echocardiography (94.6%). Fifty-five percent of survivors had at least one modifiable cardiovascular risk factor (i.e., current smoking, overweight, new/insufficiently controlled hypertension, dyslipidemia, or diabetes). Screening detected ≥ 1 CVD in 31.1% of survivors. Among survivors with available echocardiography report (n = 106), screening detected new aortic and/or mitral valve dysfunction(s) in 51.0% (with grades 3-4 in 4.9%) and impaired left ventricular ejection fraction in 10.3%. Adherence to the screening guidelines in the Dutch HL survivorship care program was reasonable to good and a substantial number of actionable (risk factors for) CVD were diagnosed. Our findings inform HL survivors at high risk of late cardiotoxicity about cardiovascular screening findings and demonstrate appropriate therapeutic actions after diagnosis of (risk factors for) CVD.

Effectiveness and Cost-Effectiveness of Survivorship Care for Survivors of Hodgkin Lymphoma (INSIGHT Study): Protocol for a Multicenter Retrospective Cohort Study With a Quasi-Experimental Design.

Hodgkin lymphoma (HL) occurs at young ages, with the highest incidence between 20 and 40 years. While cure rates have improved to 80%-90% over the past decades, survivors of HL are at substantial risk of late treatment-related complications, such as cardiovascular diseases, breast cancer, severe infections, and hypothyroidism. To reduce morbidity and mortality from late treatment effects, the Dutch Better care after lymphoma, Evaluation of long-term Treatment Effects and screening Recommendations (BETER) consortium developed a survivorship care program for 5-year survivors of HL that includes risk-based screening for and treatment of (risk factors for) late adverse events. Even though several cancer survivorship care programs have been established worldwide, there is a lack of knowledge about their effectiveness in clinical practice. The Improving Nationwide Survivorship care Infrastructure and Guidelines after Hodgkin lymphoma Treatment (INSIGHT) study evaluates whether Dutch BETER survivorship care for survivors of HL decreases survivors' burden of disease from late adverse events after HL treatment and associated health care costs and improves their quality of life. The INSIGHT study is a multicenter retrospective cohort study with a quasi-experimental design and prospective follow-up, embedded in the national BETER survivorship care infrastructure. The first BETER clinics started in 2013-2016 and several other centers started or will start BETER clinics in 2019-2024. This allows us to compare survivors who did and those who did not receive BETER survivorship care in the last decade. Survivors in the intervention group are matched to controls (n=450 per group) based on sex, age at diagnosis (±5 years), age in 2013 (±5 years), and treatment characteristics. The primary outcome is the burden of disease in disability-adjusted life years from cardiovascular disease, breast cancer, severe infections, and hypothyroidism. In a cost-effectiveness analysis, we will assess the cost of BETER survivorship care per averted or gained disability-adjusted life year and quality-adjusted life year. Secondary outcomes are BETER clinic attendance, adherence to screening guidelines, and knowledge and distress about late effects among survivors of HL. Study data are collected from a survivor survey, a general practitioner survey, medical records, and through linkages with national disease registries. The study was funded in November 2020 and approved by the institutional review board of the Netherlands Cancer Institute in July 2021. We expect to finalize recruitment by October 2024, data collection by early 2025, and data analysis by May 2025. INSIGHT is the first evaluation of a comprehensive survivorship program using real-world data; it will result in new information on the (cost-)effectiveness of survivorship care in survivors of HL in clinical practice. The results of this study will be used to improve the BETER program where necessary and contribute to more effective evidence-based long-term survivorship care for lymphoma survivors. PRR1-10.2196/55601.

Development and validation of a machine learning-based postoperative prognostic model for plasma cell neoplasia with spinal lesions as initial clinical manifestations: a single-center cohort study.

Spinal multiple myeloma (MM) and solitary plasmacytoma of bone (SPB), both plasma cell neoplasms, greatly affect patients' quality of life due to spinal involvement. Accurate prediction of surgical outcomes is crucial for personalized patient care, but systematic treatment guidelines and predictive models are lacking. This study aimed to develop and validate a machine learning (ML)-based model to predict postoperative outcomes and identify prognostic factors for patients with spinal MM and SPB. A retrospective analysis was conducted on patients diagnosed with MM or SPB from 2011 to 2015, followed by prospective data collection from 2016 to 2017. Patient demographics, tumor characteristics, clinical treatments, and laboratory results were analyzed as input features. Four types of ML algorithms were employed for model development. The performance was assessed using discrimination and calibration measures, and the Shapley Additive exPlanations (SHAP) method was applied for model interpretation. A total of 169 patients were included, with 119 for model training and 50 for validation. The Gaussian Naïve Bayes (GNB) model exhibited superior predictive accuracy and stability. Prospective validation on the 50 patients revealed an area under the curve (AUC) of 0.863, effectively distinguishing between 5-year survivors and non-survivors. Key prognostic factors identified included International Staging System (ISS) stage, Durie-Salmon (DS) stage, targeted therapy, and age. The GNB model has the best performance and high reliability in predicting postoperative outcomes. Variables such as ISS stage and DS stage were significant in influencing patient prognosis. This study enhances the ability to identify patients at risk of poor outcomes, thereby aiding clinical decision-making.

Characteristics of Long-Term Survivors With EGFR-Mutant Metastatic NSCLC

IntroductionCharacteristics of long-term survivors in EGFR-mutant (EGFRm) NSCLC are not fully understood. This retrospective analysis evaluated a multi-institution cohort of patients with EGFRm NSCLC treated in the pre-osimertinib era and sought to describe characteristics of long-term survivors. MethodsClinical characteristics and outcomes were abstracted from the electronic medical records of patients with EGFRm metastatic NSCLC who started first-line therapy before 2015. Demographics and comutations were compared between greater than or equal to 5-year survivors and less than 5-year survivors. Multivariable Cox proportional hazard and logistic regression models were used to evaluate factors associated with survival and the odds of death within 5 years, respectively. ResultsOverall, 133 patients were greater than or equal to 5-year survivors; 127 were less than 5-year survivors. Burden of pathogenic comutations including TP53 and PIK3CA was similar between greater than or equal to 5-year survivors and less than 5-year survivors. Receipt of first-line chemotherapy rather than EGFR tyrosine kinase inhibitor was similar between the groups (22% of <5-y versus 31% of ≥5-y). Baseline brain metastasis and history of smoking were associated with higher odds of death within 5 years (odds ratio = 2.16, p = 0.029 and odds ratio = 1.90, p = 0.046, respectively). Among patients without baseline brain metastases, cumulative incidence of brain metastases at 5 years was 42.3%. Both baseline and post-baseline brain metastasis were associated with worse overall survival compared with no brain metastasis (hazard ratio = 3.26, p < 0.001 and hazard ratio = 4.99, p < 0.001, respectively). ConclusionsWithin patients treated for EGFRm metastatic NSCLC before 2015, absence of brain metastasis and nonsmoking status were predictive of 5-year survival. Our findings help to define a subset of patients with EGFRm NSCLC with excellent survival outcomes who may not require intensification of initial therapy.