Post-Traumatic Stress Symptoms in Adolescent Hodgkin Lymphoma Survivors: A Report from Children's Oncology Group AHOD0031

Abstract

Purpose:

The intrusive thoughts of cancer diagnosis, treatments, re-experiencing, and avoidance associated with post-traumatic stress symptoms (PTSS) can negatively affect Hodgkin lymphoma (HL) survivors. This study investigates the associations between experiences and beliefs and PTSS among adolescent survivors of intermediate-risk HL treated on the Children's Oncology Group (COG) AHOD0031 study.

Methods:

COG AHOD0031 participants completed self-report surveys at end of therapy concerning post-treatment medical conditions, activity limitations, fatigue, future concerns, exercise, and PTSS.

Results:

One thousand one hundred ten of 1721 participants in AHOD0031 completed the first survey at a median of 6.7 months post-diagnosis (interquartile range: 5.3–11.5 months), and of these, 736 (66.3%) completed a second survey at a median of 12.4 (10.1–17.6) months following the first. The mean PTSS score (ranging from 0 to 20) was 5.5 (standard deviation [SD] = 5.1) on survey 1 and 4.4 (SD = 4.8) on survey 2. Increased fatigue (odds ratio [OR] = 1.14, p < 0.01), concerns for the future (OR = 1.13, p < 0.01), activity limitations (OR = 1.05, p < 0.01), and relapse history (OR = 2.18, p < 0.05) were associated with higher PTSS scores in the initial survey. Increased fatigue (OR = 1.16, p < 0.01), concerns for the future (OR = 1.14, p < 0.01), activity limitations (OR = 1.05, p < 0.05), and higher PTSS scores on the first survey (OR = 1.19, p < 0.01) were associated with higher PTSS scores in the subsequent survey. Longer time since diagnosis (OR = 0.85, p < 0.05; OR = 0.84, p < 0.05) was associated with lower PTSS scores on both surveys.

Conclusions:

Based on our findings, future research should examine the onset and trajectory of PTSS among HL survivors, focusing on early recognition and intervention to improve quality of life.

Introduction

As the 5-year survival rate of Hodgkin lymphoma (HL) in the pediatric population has reached 98%,¹ more emphasis has been placed on long-term morbidity, both medical and psychological, associated with disease and treatment. The experiences associated with a cancer diagnosis and treatment can be traumatic within pediatric oncology patients² and impact long-term psychosocial adjustment. Adverse psychological long-term sequelae associated with a cancer diagnosis and treatment within adolescent survivors of pediatric cancers include anxiety and post-traumatic stress symptoms (PTSS).³ Therefore, it is imperative to target risk factors of these symptoms for early mitigation to improve quality of life within pediatric survivorship.

PTSS include intrusive thoughts of re-experiencing trauma, avoidance of thoughts or places related to the trauma, and heightened arousal, differing from a formal diagnosis of post-traumatic stress disorder (PTSD). The DSM-5-TR (Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision) defines PTSD with specific criteria based on timing and severity after previous exposure to death or the threat of death, serious injury, or violence leading to these above symptoms, causing impairment in daily functioning.⁴

Although there may be overlap with other psychological pathologies, PTSS are related to past history of a traumatic event. The literature has conflicting reports as to whether pediatric and adolescent survivors of pediatric cancers have an increased risk of PTSD compared to healthy control groups⁵; however, they are more likely to have individual or clusters of symptoms of PTSS.^6,7 PTSS can have a detrimental effect on survivors' quality of life, overall developmental adjustment, and family achievement.^2,8

Currently receiving treatment, surgical treatment history, a diagnosis of cancer with a 90%–100% survival rate, not attending school, and greater PTSS at 6 months were associated with greater PTSS at 12 months among adolescent and young adult cancer patients.⁹ Among pediatric and adolescent cancer survivors, negative emotionality was associated with a higher level of PTSS and specific treatment-related medical conditions were not associated with PTSS¹⁰; however, the number of medical conditions was associated with the variance of PTSS.⁶ Female gender and less perceived social support were risk factors to developing PTSS.^11,12

This study expands on these data in a large population of similarly treated adolescent patients with HL associated with exceptional survival rates. We investigate the associations between experiences and beliefs and PTSS among adolescent survivors of intermediate-risk HL treated on the Children's Oncology Group (COG) AHOD0031 study.¹³ The COG AHOD0031 evaluated a dose-dense regimen of multiagent chemotherapy and titration of therapy based on early chemotherapy response. Specifically examining this population of HL survivors provides insight into the factors associated with PTSS and investigates how these associations may change over time.

We hypothesized that disease, patient-centered factors, slow early response to initial chemotherapy, and relapse history would be associated with higher rates of PTSS. We hypothesized that decreased frequency of physical activity, increased fatigue, limitations in activities of daily living, increased future concerns about one's health, and post-therapy medical conditions would be associated with higher PTSS.

Methods

COG AHOD0031 was approved by the National Cancer Institute and each participating institution's institutional review board. Participants enrolled from September 2002 through July 2009 were younger than 22 years, were with newly diagnosed HL, and had pathologically confirmed HL, Ann Arbor stages IB, IAE, IIB, IIAE, IIIA, or IVA with or without bulk disease and IA or IIA with bulk disease. All participants received two cycles of doxorubicin, bleomycin, vincristine, etoposide, prednisone, and cyclophosphamide (ABVE-PC) and then underwent a response evaluation, identifying rapid early responders (RERs) and slow early responders (SERs).

All RERs received an additional two cycles of ABVE-PC. RERs who were in complete remission (CR) after four cycles were randomized to either receive no additional therapy or involved-field radiation therapy (IFRT). RERs with less than CR after four cycles received IFRT. SERs after two cycles of ABVE-PC received two additional ABVE-PC cycles and were randomly assigned to also receive two cycles of dexamethasone, etoposide, cisplatin, and cytarabine (DECA). All SERs were assigned to receive IFRT.¹³

Participants enrolled in COG AHOD0031 completed self-reported end-of-therapy surveys, concerning post-therapy medical conditions (endocrine, cardiac, pulmonary, and gastrointestinal), activity limitations, fatigue, future concerns, exercise frequency, and PTSS. For patients <18 years old, a parent could have completed the survey. This survey was modified from the Childhood Cancer Survivor Study surveys to focus specifically on the outcomes associated with HL and its treatment.¹⁴ Questions were worded to limit conditions to those diagnosed after the HL diagnosis. Participants completed a second follow-up survey a year after the first. Disease and self-reported outcome data were collected by participating institutions and submitted to the COG. That data were transferred to a REDCap electronic database hosted at Vanderbilt University Medical Center.^15–17

Outcome variable and covariates

Our outcome variable was PTSS, a cumulative score of five questions tallying how often participants experienced symptoms (5-point Likert scale 0 = Not at all to 4 = Very much so) of avoidance, intrusive thoughts, or feelings of nervousness (Table 3). Covariates included fatigue, activity limitations, future concerns, exercise, and post-treatment medical conditions. Higher scores were associated with greater PTSS, but this was not designed to have clinical significance for PTSD.

Fatigue represented the cumulative score of five questions assessing how often (5-point Likert scale from Not at all to Very much so) participants experience fatigue symptoms (i.e., “How often have you needed to sleep during the day?”). Higher scores indicated increased frequency of fatigue.

Activity limitations included six questions on how long participants experienced limitations on physical activities (such as walking, carrying groceries, dressing, etc.) that ranged on a 3-point scale of Not limited at all, Limited for 3 months or less, or Limited for more than 3 months. Higher scores reflect increased activity limitations for a longer amount of time.

Future concerns represented the cumulative score of three questions inquiring of participants' concerns for future health, developing subsequent cancer, and ability to have children on a 5-point Likert scale of Not at all concerned to Very Concerned. Higher scores reflect a greater future concern.

Exercise frequency was a mean score of how many days per week each participant averaged in exercising for at least 20 minutes, which would make them sweat or breathe hard.

Post-treatment medical conditions were divided into four binary items of whether participants had any self-reported medical condition (endocrine, cardiac, pulmonary, or gastrointestinal) after being treated for HL.

Statistical analyses

Patient characteristics gathered by chart review were summarized using means and standard deviations (SDs) for continuous variables and frequencies for categorical variables. We conducted comparisons using a chi-squared test among categorical variables and a linear-model ANOVA test among continuous variables. Longitudinal comparisons were restricted to participants who completed a survey at both time points. PTSS scores were modeled using proportional odds logistic regression models. These models are typically used for an ordinal response variable; however, they also apply to analysis of a continuous outcome, and are particularly useful when the response distribution is positively skewed as was the case in our data.¹⁸ Using these models, we estimated the association between covariates and PTSS and summarized the association using odds ratios (ORs) comparing odds of scoring higher PTSS. This approach is described by Harrell¹⁹ and available in R version 4.0.²⁰ p-Value of <5% was used for statistical significance.

Results

Treatment outcomes

The treatment outcomes for this study were previously reported.¹³ To put in context for this study of PTSS, the 4-year event-free survival was 85.0% and overall survival was 97.8%.

Descriptive analyses

One thousand one hundred ten of 1721 participants on AHOD0031 completed the first survey at a median of 6.7 months post-diagnosis (quartiles: 5.3–11.5 months) and 736 participants of the initial 1110 (66.3%) completed a second survey at a median of 12.4 (10.1–17.6) months since the first one. Among those who completed survey 2 compared to nonresponders, there was no statistical difference in their age, gender, race, whether were RERs or SERs, stage of HL, or relapse (Table 1). Approximately half of the participants were female (survey 1: 542/1110, 49%; survey 2: 350/736, 48%), were on average 14.6 years old in survey 1 (SD = 3.3) and 14.5 years old in survey 2 (SD = 3.4), with a majority (survey 1: 888/1110, 86%; survey 2: 598/736, 87%) identifying as white. Additional sociodemographic information is available in Table 2.

Table 1.

Responders and Nonresponders

	Nonresponders^a (n = 374), N (%)	Responders^b (n = 736), N (%)	p
Age, years
Mean (SD)	14.7 (3.2)	14.5 (3.4)	0.38
Gender
Female	192 (51)	350 (48)	0.23
Race			0.30
White	290 (77)	598 (81)
Black	37 (10)	72 (10)
Other	17 (5)	21 (3)
Missing	30 (8)	45 (6)
HL stage			0.47
1	20 (5)	43 (6)
2	204 (55)	432 (59)
3	82 (22)	149 (20)
4	68 (18)	112 (15)
Early responders			0.79
RER	305 (82)	605 (82)
SER	69 (18)	131 (18)
Relapse	21 (6)	51 (7)	0.40

Nonresponders: only completed survey 1.

Responders: Completed both surveys 1 and 2.

HL, Hodgkin lymphoma; RER, rapid early responder; SD, standard deviation; SER, slow early responder.

Table 2.

Sociodemographics Table

	Survey 1 (n = 1110), N (%)	Survey 2 (n = 736), N (%)
Age, years
Mean (SD)	14.6 (3.3)	14.5 (3.4)
Gender
Female	542 (49)	350 (48)
Race
White	888 (80)	598 (81)
Black	109 (10)	72 (10)
Other	38 (3)	21 (3)
Missing	75 (7)	45 (6)
HL stage
1	63 (6)	43 (6)
2	636 (57)	432 (59)
3	231 (21)	149 (20)
4	180 (16)	112 (15)
Early responders
Rapid	910 (82)	605 (82)
Slow	200 (18)	131 (18)
SERs
IFRT	104 (52)	70 (53)
IFRT+DECA	96 (48)	61 (47)
Relapse	34 (3)	51 (7)
Time since diagnosis, years
Mean (SD)	0.9 (0.9)	2.1 (1.4)

DECA, dexamethasone, etoposide, cisplatin, and cytarabine; IFRT, involved-field radiation therapy.

The mean PTSS score (ranging from 0 to 20) was 5.5 (SD = 5.1) on survey 1 and 4.4 (SD = 4.8) on survey 2. Descriptive analyses of PTSS are detailed in Table 3. Descriptive analyses of fatigue, activity limitations, future concerns, current health behaviors and post-treatment medical conditions reported in survey 1 and survey 2 are detailed in Table 4. The surveys demonstrated high reliability based on the measures' internal consistency coefficients (Table 5).

Table 3.

Description of Post-Traumatic Stress Symptoms

	Survey 1: n (%)	Survey 2: n (%)
Tried to avoid thought of your cancer or treatment of your cancer?^a
Not at all	503 (45)	424 (58)
A little bit	250 (23)	140 (19)
Moderately	124 (11)	57 (8)
Quite a bit	110 (10)	55 (7)
Very much so	122 (11)	59 (8)
Had thoughts or images of your treatment for cancer come into your mind, even when you did not want them to?^b
Not at all	510 (46)	405 (55)
A little bit	316 (29)	177 (24)
Moderately	120 (11)	72 (10)
Quite a bit	102 (9)	59 (8)
Very much so	58 (5)	23 (3)
Found that certain places or sayings have reminded you of your treatment for cancer?^c
Not at all	356 (32)	274 (37)
A little bit	320 (29)	196 (27)
Moderately	173 (16)	114 (16)
Quite a bit	130 (12)	80 (11)
Very much so	128 (12)	70 (10)
Tried to avoid things that remind you of your treatment for cancer?^d
Not at all	546 (49)	434 (59)
A little bit	228 (21)	139 (19)
Moderately	104 (9)	55 (7)
Quite a bit	106 (10)	60 (8)
Very much so	125 (11)	47 (6)
Felt more nervous, jumpy, or irritable?^e
Not at all	651 (59)	493 (67)
A little bit	236 (21)	120 (16)
Moderately	103 (9)	62 (8)
Quite a bit	61 (6)	36 (5)
Very much so	56 (5)	24 (3)

Missing variables: 1 in survey 1; 1 in survey 2.

Missing variables: 4 in survey 1.

Missing variables: 3 in survey 1; 2 in survey 2.

Missing variables: 1 in survey 1; 1 in survey 2.

Missing variables: 3 in survey 1; 1 in survey 2.

Table 4.

Description of Covariates

	Question range	Survey 1 (n = 1110)	Survey 2 (n = 736)
Fatigue, mean (SD)	5–25	8.8 (4.6)	8.0 (4.0)
Activity limitations	6–18	8.9 (3.2)	8.3 (3.2)
Future concerns	3–15	9.6 (3.7)	9.2 (3.7)
Exercise frequency^a	0–7	3.0 (2.3)	3.3 (2.2)
Post-treatment medical conditions, n (%)	Reporting any conditions
Cardiac^b		89 (8.0)	70 (10)
Pulmonary		33 (3)	25 (3)
Endocrine^c		175 (16)	149 (20)
Gastrointestinal		225 (20)	179 (24)

Exercise noted as frequency of exercise per days in a week; survey 1: 62 missing; survey 2: 35 missing.

Two missing responses in survey 1.

Table 5.

Survey Reliability

	Cronbach's alpha for survey 1	Cronbach's alpha for survey 2
PTSS	0.84	0.85
Fatigue	0.91	0.89
Activity limitations	0.87	0.90
Future concerns	0.81	0.82

PTSS, post-traumatic stress symptoms.

Regression analyses

Among participants who completed the first survey, increased fatigue (OR = 1.14 [95% CI: 1.11–1.18], p < 0.01), increased concerns for the future (OR = 1.13 [95% CI: 1.09–1.16], p < 0.01), increased limitations in daily living and activities (OR = 1.05 [95% CI: 1.02–1.09], p < 0.01), and history of relapse (OR = 2.18 [95% CI: 1.20–3.97], p = 0.01) were associated with higher PTSS scores. Longer time since diagnosis (years) (OR = 0.85 [95% CI: 0.76–0.95], p = 0.01) and SER who received DECA compared to those who did not (OR = 0.53 [95% CI: 0.32–0.86], p = 0.01) were associated with lower PTSS scores (Table 6).

Table 6.

Proportional Odds Models Among Survey 1

Variables	Odds ratio	95% CI	p
Age	1.03	0.99–1.06	0.13
Female vs. Male	1.06	0.85–1.32	0.62
Race
Black vs. White	0.71	0.49–1.03	0.07
Other vs. White	0.77	0.44–1.35	0.36
Staging
2 vs. 1	0.97	0.60–1.55	0.88
3 vs. 1	1.00	0.61–1.65	1.00
4 vs. 1	1.11	0.67–1.86	0.68
Relapse	2.18	1.20–3.97	0.01
Time since diagnosis	0.85	0.76–0.95	<0.01
SER vs. rapid ER	1.00	0.76–1.31	0.99
SER receiving DECA vs. SER not receiving DECA	0.53	0.32–0.86	0.01
Fatigue	1.14	1.11–1.18	<0.01
Activity limitations	1.05	1.02–1.09	<0.01
Future concerns	1.13	1.09–1.16	<0.01
Exercise frequency	1.04	0.99–1.09	0.10
Cardiac secondary conditions	1.05	0.71–1.56	0.79
Pulmonary secondary conditions	0.60	0.32–1.13	0.11
Endocrine secondary conditions	0.95	0.71–1.27	0.72
Gastrointestinal secondary conditions	1.17	0.89–1.53	0.26

95% CI, 95% confidence interval.

Among participants who completed the follow-up survey, increased fatigue (OR = 1.16 [95% CI: 1.12–1.21], p < 0.01), increased concerns for the future (OR = 1.14 [95% CI: 1.10–1.19], p < 0.01), increased limitations in daily living and activities (OR = 1.05 [95% CI: 1.00–1.10], p < 0.05), and higher PTSS scores on the first survey (OR = 1.19 [95% CI: 1.16–1.23], p < 0.01) were associated with higher PTSS scores. Time since diagnosis and PTSS were negatively associated (OR = 0.84 [95% CI: 0.76–0.93], p < 0.01) (Table 7). Age, sex, race, stage, response to therapy, and post-treatment medical conditions were not associated with PTSS following either survey.

Table 7.

Proportional Odds Models Among Survey 2

Variables	Odds ratio	95% CI	p
Age	1.02	0.98–1.07	0.32
Female vs. Male	1.19	0.90–1.59	0.22
Race
Black vs. White	0.99	0.61–1.60	0.97
Other vs. White	0.69	0.31–1.53	0.36
Staging
2 vs. 1	1.82	0.99–3.36	0.05
3 vs. 1	1.63	0.85–3.14	0.14
4 vs. 1	1.47	0.75–2.90	0.26
Relapse	0.61	0.21–1.77	0.36
Time since diagnosis	0.84	0.76–0.93	<0.01
SER vs. RER	1.19	0.85–1.66	0.31
SER receiving DECA vs. SER not receiving DECA	0.73	0.40–1.35	0.32
Fatigue	1.16	1.12–1.21	<0.01
Activity limitations	1.05	1.00–1.10	<0.05
Future concerns	1.14	1.10–1.19	<0.01
Exercise frequency	1.00	0.94–1.06	0.92
Cardiac secondary conditions	0.92	0.58–1.46	0.72
Pulmonary secondary conditions	0.66	0.32–1.36	0.26
Endocrine secondary conditions	1.18	0.84–1.66	0.34
Gastrointestinal secondary conditions	1.01	0.74–1.39	0.94
Survey 1 PTSS	1.19	1.16–1.23	<0.01

Follow-up logistic regression analyses were conducted to assess whether there were differences in significance between the separate items within the activity limitations variable as this variable was significantly associated with increased PTSS scores in both the initial and follow-up surveys. Activity limitations of participating in sports (OR = 1.18 [95% CI: 1.01–1.38], p < 0.05) were significantly associated with increased PTSS in the baseline survey data analysis; however, it was not found to be significant in the follow-up survey analyses. In addition, since the SERs who received DECA compared to those who did not receive DECA were associated with lower PTSS scores, we ran follow-up logistic regression analyses assessing whether other types of treatment received would impact PTSS scores, such as receiving IFRT versus not receiving IFRT. There was no significant association with PTSS scores in both surveys.

Discussion

This study examined the prevalence and covariates of PTSS among adolescent HL survivors. Increased fatigue, activity limitations, and future concerns were associated with higher scores of PTSS. We did not find significant associations between early response to treatment, exercise frequency, and subsequent medical conditions with PTSS as initially predicted. Relapse was associated with PTSS as hypothesized, but only at the initial survey.

The mean PTSS score was relatively low with scoring a 5.5 (SD = 5.1) on a scale of 0–20 and 4.4 (SD = 4.8) at the 1 year follow-up. As the literature varies on how to measure PTSS and PTSS does not meet a clinical diagnosis of PTSD, it is difficult to assess how this compares to prior studies.^9,21–23 PTSS may have been overestimated in some studies and one study found it lower in pediatric oncology patients (mean of 15.5, with SD of 12.7) compared to the incidence in a control group (p = 0.002).²⁴ However, the PTSS measure and range in this study are different than ours, and thus, we cannot directly compare. We assessed PTSS over a short time period following treatment and may not be generalizable to a survivorship population as more time may need to elapse. As time since diagnosis increased, PTSS scores decreased. PTSS may peak at a certain time point and then decrease as time continues. Further research will help determine a more long-term trajectory of PTSS in this population as participants may experience other adverse health outcomes related to treatment with ongoing time.

Increased fatigue and activity limitations were associated with PTSS, expanding on present literature.²³ We speculate that fatigue and activity limitations impact one's quality of life and therefore could lead to an increased PTSS response. Limitations in sports on the baseline survey were more strongly associated with increased PTSS. The social component of playing on a sports team may factor into this association as socialization has been implicated in intending to pursue physical activity in young adult cancer survivors²⁵ and could guide future interventions for improving PTSS. Increased concerns about future health were associated with increased PTSS, likely due to enhanced emotional distress associated with increased worries about one's future.

RER versus SER was not associated with increased PTSS. In regression analyses, SERs who received augmented chemotherapy compared to SERs who received standard chemotherapy were found to have lower PTSS scores on the first survey. However, on follow-up survey, this finding was not significant. Those who were SERs, but were not randomized to augmented chemotherapy may have had increased concern for undertreatment and recurrence, and thus expressed more PTSS. As relapses on this therapy occurred early, it is possible that this concern dissipated by the follow-up survey a year later if one had not relapsed.

Among RERs who sustained a complete response, PTSS did not differ among those randomized to receive IFRT or no further treatment. Previous studies have shown that severity of illness was not associated with increased levels of PTSS.^6,9,26 One study showed that having had surgical treatment predicted greater PTSS compared to those who received staging-related surgery⁹; however, our study is unique in that it examined how differences in randomized assignments for chemotherapy and radiation therapy impacted PTSS and found a lack of an association.

History of relapse was significantly associated with higher PTSS scores in survey 1, but not in survey 2. There may be a longitudinal relationship in how relapse history predicts PTSS, contributing to the present literature as these variables were previously found to have no association.²⁷ However, as noted by the response rate, there was a significantly larger proportion of those who relapsed who did not complete survey 2 and could have influenced this finding.

Post-treatment medical conditions were not significantly associated with PTSS scores. There was an overall low prevalence for cardiac and pulmonary conditions and a slightly greater prevalence of endocrine and gastrointestinal conditions. Most of the endocrine conditions included hypothyroidism and the gastrointestinal conditions were nonspecific and mild (including constipation, diarrhea, indigestion, and heartburn). Medical sequela has been associated with increased PTSS among adolescent cancer survivors.^9,23 In Ozono et al's study,²³ medical sequela was defined as having any activity limitation and any need for special medical attention. The generally mild post-treatment conditions in our patients may not significantly impact their quality of life and may contribute less than previously thought on the impact of PTSS.

Increased PTSS scores in survey 1 predicted increased PTSS scores in survey 2, demonstrating the importance of identifying those who have increased PTSS earlier to effectively intervene. While our study demonstrated that PTSS decreased with increased time since diagnosis, psychosocial assessment is still important to consider in post-treatment follow-up. Survivors often do not have complete psychosocial follow-up care.²⁸ Interventions to target psychological outcomes among pediatric oncology survivors and their families^29–31 have showed a reduction in PTSS, highlighting how psychosocial care can be incorporated into routine survivorship follow-up. Understanding the onset and trajectory of symptoms is critical to determine the timing of the intervention. At a minimum, this study's results can help guide clinicians taking care of this population about the importance of screening for PTSS to help facilitate access to psychosocial resources.

This study focuses solely on HL survivors, which is unique compared to other studies focusing on covariates of PTSS across multiple cancers as each type of diagnosis brings about different treatment courses and potential for different complications. This analytic approach can be adopted across other HL clinical trials, and those in other disease groups, allowing for more refined assessment, and inform future surveillance guidelines. As new therapies evolve, HL patients will need to be followed to assess impact on PTSS.

Limitations

Possible limitations of this study include reliance on self-reported surveys on reported post-treatment medical conditions, and therefore participants may have misunderstood which health conditions were related to their cancer or cancer treatments. Also, with the use of the COG Long-Term Follow Up Guidelines,³² participants may have confused screening for a condition with a diagnosis with that condition. In addition, 66.3% of participants from survey 1 completed survey 2, and therefore this attrition rate may lower the generalizability to a larger intermediate-risk HL population, including as noted above for those who had relapsed.

For patients <18 years of age, surveys were often completed by parents, which could have affected self-report. Factors potentially influencing PTSS results that were not evaluated include other mental health conditions, and possible cultural influences. There was also relatively short follow-up post-therapy. There were 62 and 35 missing exercise frequency responses noted in surveys 1 and 2, respectively, possibly altering exercise frequency results.

Conclusion

History of relapse, fatigue, limitations in daily living, and future health concerns among pediatric survivors of HL were associated with PTSS. Time since diagnosis was negatively associated with PTSS. Future research should examine the peak time for PTSS to arise and its trajectory over time, focusing on early recognition and intervention to allow for improved quality of life and subsequently healthier outcomes among this population. As longer time since diagnosis is associated with decreased PTSS scores, these interventions ideally should occur close to diagnosis as patients may be more at risk for higher PTSS earlier on. It is important to recognize that the pediatric cancer experience is perceived as central to adolescent cancer survivors' identity and can be associated with both post-traumatic stress and growth symptoms.³³ Interventions should focus on targeting how to take the cancer experience and elucidate out positive responses for growth rather than solely stress symptoms.

Footnotes

Authors' Contributions

All authors made significant contributions to and reviewed the final article.

Disclaimer

The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Author Disclosure Statement

No competing financial interests exist.

Funding Information

This project was supported by National Cancer Institute grant number U10 CA98543 to the Children's Oncology Group Chair. NCTN Operations Center grant U10CA180886. NCTN Statistics & Data Center grant U10CA180899. St. Baldrick's Foundation. Clinical trial information: NCT00025259.

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