Survivors Of Adult-onset Cancer Research Articles

Fear of Cancer Recurrence in Adult Survivors of Childhood Cancer

Fear of cancer recurrence is common among survivors of adult-onset cancer and associated with increased distress, functional impairment, and health care utilization. However, little is known about the prevalence and risk factors of fear of cancer recurrence among adult survivors of childhood cancer who are also at high risk for subsequent malignant neoplasms. To characterize the prevalence of and risk factors for clinically significant fear of cancer recurrence in adult survivors of childhood cancer. This cross-sectional investigation included participants recruited from the Childhood Cancer Survivor Study, a retrospective cohort study of long-term childhood cancer survivors treated at 31 institutions between 1970 and 1999 across North America. Participants were recruited and completed psychosocial measures via online survey between October 2018 and April 2019. Cancer and treatment-related variables were abstracted from medical records. Data were analyzed from May 2023 to July 2024. Clinically significant fear of cancer recurrence was assessed via the Fear of Cancer Recurrence Inventory-Short Form. Poisson regression models estimated prevalence ratios (PRs) with 95% CIs adjusted for age and sex to examine the associations of demographic, disease, treatment, and psychosocial variables with fear of cancer recurrence. The final sample included 229 adult survivors of childhood cancer (115 female [50.2%]; mean [SD] age, 39.6 [9.9] years; mean [SD] time since diagnosis, 31.7 [8.4] years). Among survivors, 38 (16.6%; 95% CI, 11.6%-21.6%) reported clinically significant fear of cancer recurrence, and an additional 36 (15.7%) reported high fear of cancer recurrence. Clinically significant fear of cancer recurrence was associated with unemployment (PR, 2.5; 95% CI, 1.3-4.8), presence of neurologic chronic health conditions (PR, 3.3; 95% CI, 1.8-6.1), treatment with pelvic radiation (PR, 2.9; 95% CI, 1.5-5.6), and amputation or limb sparing surgery (PR, 2.4; 95% CI, 1.2-4.9). Higher risk of clinically significant fear of cancer recurrence was also associated with having either elevated anxiety or depression (PR, 2.6; 95% CI, 1.2-5.9), having both elevated (PR, 3.2; 95% CI, 1.2-8.4), and perceived poor health status (PR, 3.0; 95% CI, 3.1-9.7). Decades following treatment, one-third of childhood cancer survivors in this study reported elevated fear their cancer will recur or a subsequent malignant neoplasm will develop. Findings suggest that fear of cancer recurrence should be routinely screened, and clinically significant symptoms intervened upon as a part of survivorship care.

Comprehensive Audiologic Analyses After Cisplatin-Based Chemotherapy

Cisplatin is highly ototoxic but widely used. Evidence is lacking regarding cisplatin-related hearing loss (CRHL) in adult-onset cancer survivors with comprehensive audiologic assessments (eg, Words-in-Noise [WIN] tests, full-spectrum audiometry, and additional otologic measures), as well as the progression of CRHL considering comorbidities, modifiable factors associated with risk, and cumulative cisplatin dose. To assess CRHL with comprehensive audiologic assessments, including the WIN, evaluate the longitudinal progression of CRHL, and identify factors associated with risk. The Platinum Study is a longitudinal study of cisplatin-treated testicular cancer survivors (TCS) enrolled from 2012 to 2018 with follow-up ongoing. Longitudinal comprehensive audiologic assessments at Indiana University and Memorial Sloan Kettering Cancer Center included 100 participants without audiometrically defined profound hearing loss (HL) at baseline and at least 3.5 years from their first audiologic assessment. Data were analyzed from December 2013 to December 2022. Factors associated with risk included cumulative cisplatin dose, hypertension, hypercholesterolemia, diabetes, tobacco use, physical inactivity, body mass index, family history of HL, cognitive dysfunction, psychosocial symptoms, and tinnitus. Main outcomes were audiometrically measured HL defined as combined-ears high-frequency pure-tone average (4-12 kHz) and speech-recognition in noise performance measured with WIN. Multivariable analyses evaluated factors associated with risk for WIN scores and progression of audiometrically defined HL. Median (range) age of 100 participants at evaluation was 48 (25-67) years; median (range) time since chemotherapy: 14 (4-31) years. At follow-up, 78 (78%) TCS had audiometrically defined HL; those self-reporting HL had 2-fold worse hearing than TCS without self-reported HL (48 vs 24 dB HL; P < .001). A total of 54 (54%) patients with self-reported HL showed clinically significant functional impairment on WIN testing. Poorer WIN performance was associated with hypercholesterolemia (β = 0.88; 95% CI, 0.08 to 1.69; P = .03), lower-education (F1 = 5.95; P = .004), and severity of audiometrically defined HL (β̂ = 0.07; 95% CI, 0.06 to 0.09; P < .001). CRHL progression was associated with hypercholesterolemia (β̂ = -4.38; 95% CI, -7.42 to -1.34; P = .01) and increasing age (β̂ = 0.33; 95% CI, 0.15 to 0.50; P < .001). Importantly, relative to age-matched male normative data, audiometrically defined CRHL progression significantly interacted with cumulative cisplatin dose (F1 = 5.98; P = .02); patients given 300 mg/m2 or less experienced significantly less progression, whereas greater temporal progression followed doses greater than 300 mg/m2. Follow-up of cisplatin-treated cancer survivors should include strict hypercholesterolemia control and regular audiological assessments. Risk stratification through validated instruments should include querying hearing concerns. CRHL progression relative to age-matched norms is likely associated with cumulative cisplatin dose; investigation over longer follow-up is warranted.

Trends in mortality from secondary malignancy in the United States, 1999-2019.

11166 Background: Recent advancements in cancer diagnosis, treatment, and supportive care increased the survivorship of cancer patients. However, the risk of secondary malignancy (SM), associated most commonly with side effects of radiation and chemotherapies, has emerged as a looming threat to childhood and adult-onset cancer survivors. Recognizing the recent trends in malignancy-related deaths and the risk factors associated could assist healthcare professionals and policymakers in constructing appropriate guidelines for timely diagnosis and individual patient-dependent treatment regimens. Hence, our CDC analysis focuses on highlighting trends in mortality from SM from “1999 to 2019”. Methods: Using the deidentified death certificate data from the CDC WONDER database, we analyzed mortality trends from 1999 to 2019 for SM. Age-adjusted mortality rates (AAMRs) per 100,000 people were calculated for the total population, stratified by gender, race, age, and site of SM. Annual percent change (APC) was calculated using the Joinpoint regression software. Results: A total of 1,499,108 deaths occurred from 1999 to 2019 in the US. The overall AAMR showed a decrease from 27.5 in 1999 to 18.83 in 2007 (APC: -4.71), remained at a relatively constant level of 19.11 till 2013 (APC: 0.48), followed by a rapid rise to 23.29 in 2017 (APC: 5.37), and finally a gradual rise to 24.29 in 2019 (APC: 1.97). Men showed consistently higher AAMR than women throughout the study period between 1999 (AAMR Men: 33.31 vs Women: 23.78) and 2019 (AAMR Men: 28.03 vs Women: 21.51). Moreover, Black (AAMR: 23.89) showed the highest mortality rate, followed by Whites (AAMR: 21.46). American Indian (AAMR: 13.93), Asian (AAMR: 13.89), and Hispanic (AAMR: 15.9) showing similar mortality trends. Furthermore, AAMR increased with age, showing the highest mortality rates in patients 75+ yrs (148.3), followed by 55-74 yrs (61.6), 35-54 yrs (9.23), 15-34 yrs (0.7), and ≤ 14 yrs (0.19). More recently the greatest rise in SM from 2013-2019 was observed in adrenal glands (APC: 11.8), bone and bone marrow (APC: 8.7), kidney and renal pelvis (APC: 7.6), and small intestine (APC: 6.9). Less prominent rise was seen in all other types of SM. Conclusions: Despite recent advances in cancer treatments, SM remains one of the most common causes of death in cancer survivors. Our analysis shows that age, gender, race, and site are important factors influencing the risk of SM-related mortality. Although the risk of SM varies across the spectrum of age, findings from one age group could be translated into preventive and screening strategies across other age groups. Guidelines for survivors should be taken into account based on prior treated malignancy and the risk of future ones. Large population based studies are imperative to understand factors behind the recent rise in SM-related mortalities from 2013 onwards.

Body mass index and the risk of subsequent cancers among older cancer survivors.

12043 Background: Little is known about the etiology of second primary cancers among survivors of older adult-onset cancers. Descriptive studies have suggested that lifestyle factors, including body mass index (BMI), may be important. Here we investigated whether BMI is associated with the risk of a subsequent malignancy among older adult cancer survivors. Methods: This analysis was conducted among men and women enrolled in the Cancer Prevention Study II Nutrition cohort who were diagnosed with a first non-metastatic incident cancer between 1992 and 2015. Survivors were followed-up until 2017 for the diagnosis of a subsequent primary malignancy at a different organ to avoid the inclusion of recurrences, as their etiology may differ. Analyses were restricted to those who were younger than 85 years at their initial diagnosis. Subsequent malignancies were included if they were diagnosed at least 60 days after the first cancer. Outcomes of interest were second cancers and obesity-related second cancer as defined by the IARC. BMI at the time or before their first cancer was self-reported (median: 1.3 years from BMI report to diagnosis). Participants who were underweight (BMI&lt;18.5 kg/m2) were excluded. Cox regression was used to compute hazard ratios (HR) and 95% confidence intervals (CI) to estimate the risk of second cancers associated with BMI. Models were adjusted for age, sex, race, diagnosis year, and stage of the first cancer. Results: This cohort included 26,894 participants diagnosed with a first cancer. The median age at diagnosis of the first cancer was 72.5 years (interquartile range (IQR): 67.7, 77.0). Most participants were women (59%), overweight or obese (60%) and diagnosed with localized disease (71%). During a median of follow-up of 7.5 years (IQR: 3.2, 13.1), 3,748 participants were diagnosed with a second cancer, including 1,140 obesity-related second cancers. Approximately 90% of second malignancies were diagnosed at least 1 year, and 70% at least 5 years after the first cancer. Compared with cancer survivors whose BMI was in the normal range (18.5≤BMI&lt;25), those who were overweight or obese were at an increased risk of any second cancer (25≤BMI&lt;30: HR=1.12, 95% CI: 1.05, 1.21; BMI≥30: HR=1.29, 95% CI: 1.18, 1.42) and BMI-related cancers (25≤BMI&lt;30: HR=1.37, 95% CI: 1.20, 1.57; BMI≥30: HR=1.60, 95% CI: 1.36, 1.88). In particular, obesity was associated with increased risks of breast (HR=1.43, 95% CI: 1.03, 1.98) and colorectal (HR=1.91, 95% CI: 1.42, 1.56) second cancers. Conclusions: Older adult cancer survivors who were overweight or obese at the time of their first cancer diagnosis were at higher risk of developing a second cancer, especially a BMI-related cancer. These findings have important public health implications given the high prevalence of overweight and obesity in this population. Weight loss strategies should be considered and heightened awareness of second cancers among physicians of older cancer survivors.

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 17070: Dyslipidemia Prevalence Among a Diverse Cohort of Childhood, Adolescent and Young Adult Cancer Survivors

Background: In the general population, dyslipidemia impacts 36% of adults between the ages of 20 and 29 years. Among survivors of childhood, adolescent, and young adult-onset cancer (C-AYAs), the prevalence of dyslipidemia in racially diverse cohorts as well as our understanding of which measured fats are most commonly abnormal are limited. Question: Among a diverse group of C-AYAs, what is the prevalence of dyslipidemia and which fats are most contributory? Methods: Individuals diagnosed with cancer at age ≤39 years and treated with anthracycline based chemotherapy between 2010-2022 were identified. Depending on age at time of collection, post-treatment lipid panels were analyzed according to AAP (&lt;20 years) or ACC/AHA (≥20 years) guidelines. Non-fasting panels were included, in accordance with ACC/AHA guidelines. The prevalence of dyslipidemia and median values for measured fats were determined. Non-parametric testing was used to examine associations between dyslipidemia, age, and race. Results: Among a diverse (40% Black, 52% White) cohort of C-AYAs (227 total) with a median current age of 25 years (interquartile range (IQR) 20-36 years) and median total doxorubicin isotoxic equivalents of 200mg/m 2 (IQR 120-300 mg/m 2 ), the prevalence of dyslipidemia was 55%. Prevalence of dyslipidemia was not associated with race (Black 55%, White 64%, Other 44%, p=0.281) or age (&lt;20 years 51%, ≥20 years 64%, p = 0.055). Among Black and White subjects, HDL was most commonly abnormal (Black 42%, White 38%), followed by triglycerides (TG) (Black 29%, White 41%). Median TG levels were significantly lower among Black individuals ≥20 years compared with White individuals (117 mg/dL vs 143 mg/dL, p = 0.030). Conclusions: Among a diverse group of C-AYAs, dyslipidemia was highly prevalent even at a younger age (&lt;20 years). Race was not associated with prevalence of dyslipidemia. Dyslipidemia was primarily driven by HDL and TG abnormalities, fats associated with metabolic syndrome.

Description of survivorship recommendations in NCCN guidelines.

483 Background: The National Comprehensive Cancer Network (NCCN) issues evidence-based guidelines to ensure that all patients receive preventive, diagnostic, treatment, and supportive services that are most likely to lead to optimal outcomes. The information offered by these guidelines is used as the standard for clinical management and policy in cancer care. This study aimed to assess the content of survivorship recommendations in the NCCN guidelines. Methods: In April 2023, a total of 59 guidelines were downloaded from the NCCN website and assessed for survivorship recommendations and information provided. The guidelines were aimed at both adults and children with cancer. Results: Among the evaluated NCCN cancer guidelines (n=59), only 20% included a dedicated survivorship section. Of the 12 guidelines with survivorship sections, all targeted survivors of adult-onset cancer. Half of these guidelines featured only general survivorship recommendations, for example, gynecological and colorectal cancers. When cancer survivorship sections were included, the most common domains were surveillance/management of late and long-term physical effects (92%), health promotion (92%), and psychosocial effects (75%). Surveillance for recurrences/new cancers and chronic disease management were less common (58% and 50%, respectively). Surprisingly, only 47% of guidelines without survivorship sections referred to other resources for the care of cancer survivors (including the NCCN survivorship guideline). Conclusions: The findings indicate that less than a quarter of NCCN guidelines include a section dedicated to cancer survivorship recommendations and less than half of the guidelines without survivorship sections referred to other resources for the care of cancer survivors. Though NCCN has a dedicated survivorship guideline, the lack of survivorship recommendations in disease-based guidelines shows a gap in the comprehensive provision of survivorship guidance. Standardization of survivorship care recommendations across all NCCN guidelines is needed.

Association of first primary cancer with risk of subsequent primary cancer among survivors of adult-onset cancers in Kentucky and Appalachian Kentucky.

Appalachia is a region with significant cancer disparities in incidence and mortality compared to Kentucky and the United States. However, the contribution of these cancer health disparities to subsequent primary cancers (SPCs) among survivors of adult-onset cancers is limited. This study aimed to quantify the overall and cancer type-specific risks of SPCs among adult-onset cancer survivors by first primary cancer (FPC) types, residence and sex. This retrospective cohort study from the Kentucky Cancer Registry included 148,509 individuals aged 20-84 years diagnosed with FPCs from 2000-2014 (followed until December 31, 2019) and survived at least 5 years. Expected numbers of SPC were derived from incidence rates in the Kentucky population; standardized incidence ratio (SIR) compared with those expected in the general Kentucky population. Among 148,509 survivors (50.2% women, 27.9% Appalachian), 17,970 SPC cases occurred during 829,530 person-years of follow-up (mean, 5.6 years). Among men, the overall risk of developing any SPCs was statistically significantly higher for 20 of the 30 FPC types, as compared with risks in the general population. Among women, the overall risk of developing any SPCs was statistically significantly higher for 20 of the 31 FPC types, as compared to the general population. The highest overall SIR were estimated among oral cancer survivors (SIR, 2.14 [95% CI, 1.97-2.33] among men, and among laryngeal cancer survivors (SIR, 3.62 [95% CI, 2.93-4.42], among women. Appalachian survivors had significantly increased risk of overall SPC and different site specific SPC when compared to non-Appalachian survivors. The highest overall SIR were estimated among laryngeal cancer survivors for both Appalachian and non-Appalachian residents (SIR, 2.50: 95%CI, 2.10-2.95; SIR, 2.02: 95% CI, 1.77-2.03, respectively). Among adult-onset cancer survivors in Kentucky, several FPC types were significantly associated with greater risk of developing an SPC, compared with the general population. Risk for Appalachian survivors was even higher when compared to non-Appalachian residents, but was not explained by higher risk of smoking related cancers. Cancers associated with smoking comprised substantial proportions of overall SPC incidence among all survivors and highlight the importance of ongoing surveillance and efforts to prevent new cancers among survivors.

Exploring the independent association of employment status to cancer survivors’ health-related quality of life

BackgroundHaving a job has been associated with better Health-Related Quality of Life (HRQOL) in cancer survivors. However, the sociodemographic and disease-related profiles characterizing the survivors being employed and those having better HRQOL largely overlap. The present study aims to discern the degree to which employment status is independently associated with cancer survivors’ HRQOL or if it mainly reflects the impact of other sociodemographic and cancer-related variables.MethodsCross-sectional study on a heterogeneous sample of 772 working-age survivors of adult-onset cancer. An instrument specifically designed to assess HRQOL in cancer survivors and Multivariate Variance Analysis (MANOVA) were used.ResultsSurvival phase, cancer type, and employment status showed the main effects on cancer survivors’ HRQOL. In particular, being employed (vs unemployed) had the greatest positive association with HRQOL, affecting ten of the twelve HRQOL domains considered. Also, interaction effects highlighted the role of age (younger) and marital status (single) as risk factors for a greater negative impact of variables affecting the survivor’s HRQOL.ConclusionsThe application of a multivariate methodology sheds new light on two relevant issues for the cancer survivor’s HRQOL: (i) the existence of differences between diagnostic groups that are not attributed to other variables such as sex, and (ii) the important and independent role that employment status plays. Comprehensive cancer survivorship care should focus more on high-risk groups and include having a job as an essential aspect to consider and prompt. The fact that the employment status is susceptible to change represents a valuable opportunity to care for the wellbeing of this population.

Myocardial Strain during Surveillance Screening Is Associated with Future Cardiac Dysfunction among Survivors of Childhood, Adolescent and Young Adult-Onset Cancer.

Cardiovascular disease is a leading contributor to mortality among childhood, adolescent and young adult (C-AYA) cancer survivors. While serial cardiovascular screening is recommended in this population, optimal screening strategies, including the use of echocardiography-based myocardial strain, are not fully defined. Our objective was to determine the relationship between longitudinal and circumferential strain (LS, CS) and fractional shortening (FS) among survivors. This single-center cohort study retrospectively measured LS and CS among C-AYAs treated with anthracycline/anthracenedione chemotherapy. The trajectory of LS and CS values over time were examined among two groups of survivors: those who experienced a reduction of >5 fractional shortening (FS) units from pre-treatment to the most recent echocardiogram, and those who did not. Using mixed modeling, LS and CS were used to estimate FS longitudinally. A receiver operator characteristic curve was generated to determine the ability of our model to correctly predict an FS ≤ 27%. A total of 189 survivors with a median age of 14 years at diagnosis were included. Among the two survivor groups, the trajectory of LS and CS differed approximately five years from cancer diagnosis. A statistically significant inverse relationship was demonstrated between FS and LS -0.129, p = 0.039, as well as FS and CS -0.413, p < 0.001. The area under the curve for an FS ≤ 27% was 91%. Among C-AYAs, myocardial strain measurements may improve the identification of individuals with cardiotoxicity, thereby allowing earlier intervention.

Sexual Health Outcomes of Adolescent and Young Adult Colorectal Cancer Survivors and Their Partners: Protocol of a Dyadic Mixed Methods Study

Sexual dysfunction represents a critical aspect of quality of life for adolescent and young adult cancer survivors. Studies have consistently documented that adolescents and young adults report greater psychological and physical morbidity than older survivors and healthy peers, including elevated rates of sexual dysfunction, often accompanied by lower satisfaction with sex life and delays in meeting sexual milestones. Moreover, sexual dysfunction, body image concerns, and fertility status affect their confidence in being both physically and emotionally intimate. Despite this evidence, limited research has investigated the influence of psychosocial and interpersonal factors on sexual health outcomes reported by this group. This constitutes a significant gap in the provision of comprehensive sexual health care for adolescent- and young adult-onset cancer survivors, especially since greater emphasis has been recently placed on the biopsychosocial model of sexuality and dyadic approaches to intervention and treatment. In comparison to other cancer types, the incidence of colorectal cancer (CRC) has been increasing at an alarming rate for the adolescent and young adult group. Patients with early-onset CRC experience elevated rates of sexual dysfunction, psychological distress, and social and physical burden, often resulting from issues with bowel control, incontinence, and body image. This study uses an explanatory sequential mixed methods approach to (1) characterize sexual function, sexual distress, dyadic coping, infertility-related distress, relationship and mental health outcomes of adolescent and young adult CRC survivors within the first 5 years post diagnosis and their partners; (2) examine the reciprocal influence of sexual function and dyadic coping behaviors on sexual distress; and (3) identify interpersonal or couple characteristics associated with coping with sexual dysfunction and its associated distress. Participating couples (n=60) will complete a quantitative web-based survey investigating sexual function, sexual distress, dyadic coping, infertility-related distress, emotional functioning, relationship satisfaction, and body image (cancer survivors only). A subset of 20 couples will participate in an in-depth dyadic interview with 2 members of the research team to further explore couple-based strategies implemented to cope with cancer-related sexual dysfunction and distress. The study received institutional review board approval. Recruitment and enrollment of couples began in July 2022. Results will provide a deeper understanding of the challenges couples experience as they navigate sexual intimacy after CRC treatment by highlighting the role of interpersonal processes. These findings will inform a dyadic intervention for young couples at risk of greater sexual distress in the aftermath of CRC. DERR1-10.2196/41831.

Cisplatin-induced tinnitus (CIS-TINN) and patient-reported outcomes in adult-onset cancer survivors.

e24089 Background: Cisplatin is one of the most used cytotoxic drugs worldwide, but few studies have comprehensively evaluated CIS-TINN in adult-onset cancer survivors. It is critical to identify survivors with high degrees of handicap and related risk factors, as tinnitus (TINN) is strongly related to adverse health outcomes (AHO) including reduced quality of life, and poorer physical and mental health. Methods: Eligible cisplatin-treated testicular cancer survivors (TCS) (aged &lt; 60 y at diagnosis) completed comprehensive, validated health surveys, including the 20-item Tinnitus Primary Function Questionnaire (TPFQ). TPFQ assesses the 4 main TINN-impaired domains (see Table), each with a response metric of 0% (no interference) to 100% interference by TINN, with final impairment groupings of 0-16% (none/minimal), 17-42% (mild/moderate), and 43-100% (significant). TPFQ measures were compared by 2-sided signed-rank tests. Multinomial logistic regression models (adjusted for age, income, education, yrs since therapy, cisplatin dose, BMI, smoking, hypertension, and hearing loss (HL)) tested for associations with TINN severity. Results are shown as OR [95% CI], p-value. Results: Among 213 TCS [median age 46 y (IQR: 38-52 y); median time since therapy: 10.6 y (IQR: 6.8-16.6 y)], the most common AHOs were CIS-TINN (60%), and HL (60%). For TCS with CIS-TINN, the mean degree of reported interference across all TPFQ domains was 21% (median: 15, IQR: 3-33). TCS with CIS-TINN reported significantly greater interference with emotion (median: 22, range 5-40) than with concentration (median 13, IQR: 1.0-37, p = .004), hearing (median: 10, IQR: 0-30, p &lt; .001), and sleep (median: 2.4, IQR: 0-21, p &lt; .001). Conclusions: Following cisplatin chemotherapy, CIS-TINN is a leading AHO and often reported with HL and reduced quality of life. Severe CIS-TINN was associated with greater handicap on the TPFQ as well as with depression, cognitive dysfunction, and hearing aid use. Overall, however, TCS with CIS-TINN and HL reported underutilization of hearing aids.[Table: see text]

Impact of cisplatin-induced hearing loss (CIHL) on patient-reported social and emotional functioning.

12120 Background: Cisplatin is one of the most commonly used ototoxic drugs, but no study has quantified the handicap imposed by CIHL in U.S. adult-onset cancer survivors. Identification of survivors with high degrees of handicap and related risk factors is vital, as hearing loss (HL) in the general population is strongly related to adverse health outcomes, including cognitive decline, dementia, and poor mental health and social well-being. Methods: Eligible testicular cancer survivors (TCS) (age &lt; 60 y at diagnosis, given first line cisplatin) completed comprehensive health surveys, including the validated 25-item Hearing Handicap Inventory for Adults (HHIA). HHIA quantifies emotional (13 items) and social difficulties (12 items) related to HL; for each scale (0-100%), based on their responses, TCS were grouped into 3 handicap levels: 0-16% (none/minimal), 17-42% (mild/moderate), and 43-100% (significant) following HHIA recommendations. A Spearman correlation evaluated the associations between increasing HL severity and HHIA group. The association between HL and reported cognitive dysfunction was evaluated by a logistic regression analysis adjusted for age, income, education, yrs since therapy, cisplatin dose, BMI, smoking, and hypertension, with results presented as OR[CI], p-value. Results: Among 213 TCS [median age at evaluation, 46 y (IQR: 38-52 y); median time since cisplatin completion, 10.6 y (IQR: 6.8-16.6 y)], CIHL was reported by 127 TCS (60%). Of TCS with CIHL, 31% reported some degree of related handicap (for total HHIA scale: 13% TCS and 18% TCS reporting mild/moderate and significant handicap, respectively). HL severity was significantly correlated with handicap level in all domains (social, ρ = 0.85, p &lt;.001; emotional, ρ = 0.72, p &lt;.001; and total, ρ = 0.81, p &lt;.001). Cognitive dysfunction was more commonly reported by TCS with CIHL than TCS without (35% and 22%, p =.049). HL was a significant independent predictor of cognitive dysfunction, 2.20 [1.09-4.47], p =.028. Since many patients with HL in the general population report tinnitus (TINN), and TINN may suggest a worse HL phenotype, we additionally adjusted for TINN severity and found a significant independent association for TINN and cognitive dysfunction, 1.49 [1.05-2.11], p = 0.027. Despite these outcomes, only 10% of TCS with HL used hearing aids (n = 13). Conclusions: After cisplatin chemotherapy, 60% TCS report CIHL, and TCS with CIHL report poorer social and emotional function. One in 5 TCS with CIHL reported significant overall handicap. Despite these outcomes, the low prevalence of hearing aid use suggests a potential clinical intervention that could improve social and emotional well-being. If confirmed, the possible association between CIHL with TINN and cognitive dysfunction may be of particular interest, as the Lancet Commission on Dementia Prevention (2020) identified untreated HL as a key modifiable risk factor.

Ototoxicity After Cisplatin-Based Chemotherapy: Factors Associated With Discrepancies Between Patient-Reported Outcomes and Audiometric Assessments.

To provide new information on factors associated with discrepancies between patient-reported and audiometrically defined hearing loss (HL) in adult-onset cancer survivors after cisplatin-based chemotherapy (CBCT) and to comprehensively investigate risk factors associated with audiometrically defined HL. A total of 1410 testicular cancer survivors (TCS) ≥6 months post-CBCT underwent comprehensive audiometric assessments (0.25 to 12 kHz) and completed questionnaires. HL severity was defined using American Speech-Language-Hearing Association criteria. Multivariable multinomial regression identified factors associated with discrepancies between patient-reported and audiometrically defined HL and multivariable ordinal regression evaluated factors associated with the latter. Overall, 34.8% of TCS self-reported HL. Among TCS without tinnitus, those with audiometrically defined HL at only extended high frequencies (EHFs) (10 to 12 kHz) (17.8%) or at both EHFs and standard frequencies (0.25 to 8 kHz) (23.4%) were significantly more likely to self-report HL than those with no audiometrically defined HL (8.1%) [odds ratio (OR) = 2.48; 95% confidence interval (CI), 1.31 to 4.68; and OR = 3.49; 95% CI, 1.89 to 6.44, respectively]. Older age (OR = 1.09; 95% CI, 1.07 to 1.11, p < 0.0001), absence of prior noise exposure (OR = 1.40; 95% CI, 1.06 to 1.84, p = 0.02), mixed/conductive HL (OR = 2.01; 95% CI, 1.34 to 3.02, p = 0.0007), no hearing aid use (OR = 5.64; 95% CI, 1.84 to 17.32, p = 0.003), and lower education (OR = 2.12; 95% CI, 1.23 to 3.67, p = 0.007 for high school or less education versus postgraduate education) were associated with greater underestimation of audiometrically defined HL severity, while tinnitus was associated with greater overestimation (OR = 4.65; 95% CI, 2.64 to 8.20 for a little tinnitus, OR = 5.87; 95% CI, 2.65 to 13.04 for quite a bit tinnitus, and OR = 10.57; 95% CI, 4.91 to 22.79 for very much tinnitus p < 0.0001). Older age (OR = 1.13; 95% CI, 1.12 to 1.15, p < 0.0001), cumulative cisplatin dose (>300 mg/m2, OR = 1.47; 95% CI, 1.21 to 1.80, p = 0.0001), and hypertension (OR = 1.80; 95% CI, 1.28 to 2.52, p = 0.0007) were associated with greater American Speech-Language-Hearing Association-defined HL severity, whereas postgraduate education (OR = 0.58; 95% CI, 0.40 to 0.85, p = 0.005) was associated with less severe HL. Discrepancies between patient-reported and audiometrically defined HL after CBCT are due to several factors. For survivors who self-report HL but have normal audiometric findings at standard frequencies, referral to an audiologist for additional testing and inclusion of EHFs in audiometric assessments should be considered.

Hearing loss after cisplatin-based chemotherapy: Patient-reported outcomes versus audiometric assessments.

5016 Background: Although pure-tone audiometry is the gold standard to evaluate hearing loss (HL), patient-reported outcomes are practically more time and cost effective. However, no data exist on factors associated with discrepancies between patient-reported and audiometrically-defined HL in adult-onset cancer survivors after cisplatin-based chemotherapy (CBCT); and few comprehensive assessments of factors associated with audiometrically-defined HL have been conducted. Methods: A total of 1,410 testicular cancer survivors (TCS) ≥6 months post-CBCT completed comprehensive audiometric assessments (0.25-12 kHz) and detailed questionnaires of sociodemographic, clinical, and health behaviors. Audiometrically-defined HL severity was defined using American Speech-Language-Hearing Association (ASHA) criteria. Multivariable multinomial logistic regression identified factors associated with discrepancies (overestimation and underestimation vs. concordance), between patient-reported and audiometrically-defined HL and multivariable ordinal logistic regression evaluated factors associated with the HL severity. Results: Overall, 34.8% of TCS self-reported HL, while 77.8% had audiometrically-defined HL. Among TCS without tinnitus, those with audiometrically-defined HL at only extended high frequencies (EHFs) (10-12 kHz) (17.8%) or at both EHFs and standard frequencies (0.25-8 kHz) (23.4%) were significantly more likely to self-report HL than those with no audiometrically-defined HL (8.1%) (OR = 2.48; 95%CI, 1.31-4.68 and OR = 3.49; 95%CL,1.89-6.44, respectively). Older age (OR = 1.09; P&lt; 0.0001), absence of prior noise exposure (OR = 1.40; P= 0.02), and mixed/conductive HL (OR = 2.01; P= 0.0007) were associated with greater underestimation of audiometrically-defined HL severity. Hearing aid use (OR = 0.18; P= 0.003) and higher education ( P= 0.004) were associated with less underestimation of audiometrically-defined HL severity, while tinnitus was associated with greater overestimation ( P&lt; 0.0001). Older age (OR = 1.13; P&lt; 0.0001), cumulative cisplatin dose ( &gt; 300 mg/m2, OR = 1.47; P= 0.0001), and hypertension (OR = 1.80; P= 0.0007) were associated with greater ASHA-defined HL severity, whereas post-graduate education (OR = 0.58; P= 0.005) was associated with less severe HL. Conclusions: Discrepancies between patient-reported and audiometrically-defined HL after CBCT are associated with several factors including age, education, tinnitus, prior noise exposure, use of hearing aids, and conductive HL. Understanding these factors will help clinicians to better interpret self-reported HL as a surrogate for audiometric assessments. For survivors who self-report HL, but have normal audiometric findings at standard frequencies, referral to an audiologist for additional testing and inclusion of EHFs in audiometric assessments, should be considered.

Subsequent primary cancers among survivors of adolescent and young adult onset cancers in the United States.

10604 Background: Adolescent and young adult (AYA) cancer survivors are at increased risk of subsequent primary cancer (SPC); however, a comprehensive examination of risk patterns across cancer types is lacking in the U.S. Methods: SPC incidence and mortality was calculated among &gt;1-year cancer survivors aged 15 to 39 years at first primary cancer (FPC) diagnosis during 1992-2016 in 12 Surveillance, Epidemiology, and End Results registries. Rates were expressed as number of cases/deaths per 10,000 person-years and compared with those expected in the general population using standardized incidence (SIR) and standardized mortality ratios (SMR). Results: Among 202,440 survivors of AYA-onset cancers (mean age at FPC diagnosis, 31.8 years; 60.7% women), 6,675 SPC cases (34.3 per 10,000) and 3,786 SPC deaths (19.4 per 10,000) occurred during 1,955,119 person-years of follow-up (mean, 9.7 years), corresponding to an SIR of 1.58 (95%CI = 1.54-1.62) and SMR of 4.19 (95%CI = 4.06-4.33. In men, overall incidence and mortality SPC rates were statistically significantly higher for each of 21 FPC types compared with risks in the general population, except for thyroid cancer mortality. In women, risk was statistically significantly higher for 14/23 FPC types for incidence and 19/23 FPC types for mortality. SIRs were highest in survivors of pancreatic cancer (SIR = 5.68, 95% CI = 2.94-9.93; 84 per 10,000), Kaposi sarcoma (SIR = 5.15, 95%CI = 4.62-5.73; 116 per 10,000) and liver cancer (SIR = 4.97, 95%CI = 2.57-8.68; 68.4 per 10,000) in men, and acute lymphoid leukemia (SIR, 3.27, 95% CI = 2.22-4.64; 49.5 per 10,000), Hodgkin lymphoma (SIR = 2.47, 95% CI = 2.22-2.73; 51.6 per 10,000), and bone sarcoma (SIR = 2.41, 95%CI = 1.80-3.16; 47.6 per 10,000) in women. SMRs were highest in survivors of pancreatic cancer, acute lymphoid leukemia, and stomach cancer in men, and liver cancer, acute lymphoid leukemia, and soft tissue sarcoma in women. Conclusions: Overall and type-specific risk patterns of SPCs among AYA cancer survivors differ considerably across FPC type, highlighting the need for targeted approaches for cancer prevention and surveillance in survivorship care planning.

Speech perception 30 years after cisplatin-based chemotherapy in adults: limited clinical relevance of long-term ototoxicity?

Background Cisplatin-based chemotherapy (CBCT) can cause high-frequency hearing loss, but little is known about the development and clinical relevance of this hearing loss in survivors of adult-onset cancer with very long-term follow-up. This case-control study investigates hearing and speech perception both in quiet and with background noise 30-years after CBCT. Patients and methods One-hundred-and-one patients (Cases) who received CBCT for testicular cancer between 1980 and 1994 were assessed with pure-tone audiometry (.125 − 8 kHz) and speech perception tests including hearing in noise test (HINT). Self-reported hearing and tinnitus was scored by participants. Results were compared with 30 age-matched controls. Results The median age of Cases and Controls was 60 (46 − 83) and 61 years (51 − 74), respectively. The median observation time for Cases was 30 years (22 − 37). Compared with Controls, Cases had 8 and 19 dB worse age-adjusted high-frequency hearing at 6 and 8 kHz, respectively (p <.05), while thresholds at lower frequencies did not differ. All but four Cases reached 100% speech perception with basic speech audiometry. There was no difference between Cases and Controls in speech perception neither in quiet nor with both speech and background noise from the front, although the within-group variance was greater among Cases. Cases scored slightly worse with speech from front and noise from either side. Self-reported hearing loss (both hearing loss in general and specifically with background noise), and tinnitus were about three times more common among Cases compared with Controls. Conclusions Cisplatin causes high-frequency hearing loss, but speech perception tests performed both in quiet and in background noise 30 years post-treatment indicate that the clinical relevance is limited for most patients. Few patients develop severe hearing loss that requires rehabilitation but it is important to identify these patients. Self-reported hearing loss and tinnitus were more common among Cases compared with Controls.

Association of First Primary Cancer With Risk of Subsequent Primary Cancer Among Survivors of Adult-Onset Cancers in the United States

The number of cancer survivors who develop new cancers is projected to increase, but comprehensive data on the risk of subsequent primary cancers (SPCs) among survivors of adult-onset cancers are limited. To quantify the overall and cancer type-specific risks of SPCs among adult-onset cancer survivors by first primary cancer (FPC) types and sex. A retrospective cohort study from 12 Surveillance, Epidemiology, and End Results registries in the United States, that included 1 537 101 persons aged 20 to 84 years diagnosed with FPCs from 1992-2011 (followed up until December 31, 2017) and who survived at least 5 years. First primary cancer. Incidence and mortality of SPCs per 10 000 person-years; standardized incidence ratio (SIR) and standardized mortality ratio (SMR) compared with those expected in the general population. Among 1 537 101 survivors (mean age, 60.4 years; 48.8% women), 156 442 SPC cases and 88 818 SPC deaths occurred during 11 197 890 person-years of follow-up (mean, 7.3 years). Among men, the overall risk of developing any SPCs was statistically significantly higher for 18 of the 30 FPC types, and risk of dying from any SPCs was statistically significantly higher for 27 of 30 FPC types as compared with risks in the general population. Among women, the overall risk of developing any SPCs was statistically significantly higher for 21 of the 31 FPC types, and risk of dying from any SPCs was statistically significantly higher for 28 of 31 FPC types as compared with risks in the general population. The highest overall SIR and SMR were estimated among survivors of laryngeal cancer (SIR, 1.75 [95% CI, 1.68-1.83]; incidence, 373 per 10 000 person-years) and gallbladder cancer (SMR, 3.82 [95% CI, 3.31-4.39]; mortality, 341 per 10 000 person-years) among men, and among survivors of laryngeal cancer (SIR, 2.48 [95% CI, 2.27-2.72]; incidence, 336 per 10 000 person-years; SMR, 4.56 [95% CI, 4.11-5.06]; mortality, 268 per 10 000 person-years) among women. Substantial variation existed in the associations of specific types of FPCs with specific types of SPC risk; however, only a few smoking- or obesity-associated SPCs, such as lung, urinary bladder, oral cavity/pharynx, colorectal, pancreatic, uterine corpus, and liver cancers constituted considerable proportions of the total incidence and mortality, with lung cancer alone accounting for 31% to 33% of mortality from all SPCs. Among survivors of adult-onset cancers in the United States, several types of primary cancer were significantly associated with greater risk of developing and dying from an SPC, compared with the general population. Cancers associated with smoking or obesity comprised substantial proportions of overall SPC incidence and mortality among all survivors and highlight the importance of ongoing surveillance and efforts to prevent new cancers among survivors.

Clinical and Genome-Wide Analysis of Multiple Severe Cisplatin-Induced Neurotoxicities in Adult-Onset Cancer Survivors.

Cisplatin is a first-line chemotherapeutic for many cancers, but causes neurotoxicity including hearing loss, tinnitus, and peripheral sensory neuropathy. However, no study has comprehensively characterized risk factors for developing multiple (>1) severe neurotoxicities. The relationship between multiple severe neurotoxicities and age, cumulative cisplatin dose, medical history, and lifestyle/behavioral factors was evaluated in 300 cisplatin-treated testicular cancer survivors using logistic regression. Case-control genome-wide association study (GWAS; cases, n = 104 and controls, n = 196) was also performed. Age at clinical examination (P = 6.4 × 10-16) and cumulative cisplatin dose (P = 5.4 × 10-4) were positively associated with multiple severe neurotoxicity risk, as were high serum platinum levels (P = 0.02), tobacco use (ever smoker, P = 0.001 and current smoker, P = 0.002), and hypertension (P = 0.01) after adjustment for age and cumulative cisplatin dose. Individuals with multiple severe neurotoxicities were more likely to experience dizziness/vertigo (P = 0.01), Raynaud phenomenon (P = 3.7 × 10-9), and symptoms consistent with peripheral motor neuropathy (P = 4.3 × 10-14) after age and dose adjustment. These patients also reported poorer overall health (P = 2.7 × 10-5) and a greater use of psychotropic medications (P = 0.06). GWAS identified no genome-wide significant SNPs. Gene-based association analysis identified RGS17 (P = 3.9 × 10-5) and FAM20C (P = 5.5 × 10-5) as near genome-wide significant. Decreased FAM20C expression was associated with increased cisplatin sensitivity in tumor cell lines. Certain survivors are more susceptible to cisplatin-induced neurotoxicity, markedly increasing likelihood of developing numerous neuro-otological symptoms that affect quality of life. Genome-wide analysis identified genetic variation in FAM20C as a potentially important risk factor.

Fatigue-Related Cognitive-Behavioral Factors in Survivors of Childhood Cancer: Comparison with Chronic Fatigue Syndrome and Survivors of Adult-Onset Cancer.

Purpose: Cancer-related fatigue is a burdensome late effect of cancer treatment. A pilot study showed the effectiveness of cognitive-behavioral therapy (CBT) in fatigued survivors of childhood cancer (CCS). The aim of this study is to investigate whether the six cognitive-behavioral factors that are addressed during CBT differ in CCS compared with patients with chronic fatigue syndrome (CFS) and survivors of adult-onset cancer (ACS). Levels of self-esteem, optimism, and depressive symptoms, variables that are also related to fatigue, were also compared between groups. Methods: Retrospective analyses were performed on 34 CCS (ages 11-42 years), 102 patients with CFS, and 95 ACS who were referred for evaluation of severe fatigue. Fatigue severity, possible cognitive-behavioral fatigue maintaining factors, depressive symptoms, self-esteem, and optimism were assessed using questionnaires and actigraphy. Results: No significant differences were found in the factors coping with the experience of having had cancer, fear of cancer recurrence, physical activity, and in levels of self-esteem and optimism. CCS attributed their fatigue significantly more often to psychosocial causes and reported fewer problems in sleep/rest compared with patients with CFS. Compared with ACS, CCS reported significantly more social support, more problems in sleep/rest, and more depressive symptoms. Conclusions: There is substantial overlap in cognitive-behavioral factors that can maintain fatigue between CCS and CFS patients or ACS. Also differences were found regarding attribution of fatigue, the sleep/rest pattern, social support, and depressive symptoms that might have clinical implications when CBT for fatigue is provided to CCS.