Abstract
Background/Objective:
Pediatric HSCT patients are at an increased risk for skin cancers. Sun exposure is a significant modifiable environmental risk factor. While patient education on sun protection and avoidance behaviors with regular dermatology evaluations are crucial for pediatric HSCT patients, the real-life practice of these sun protection recommendations in this patient population compared to their peers is unknown.
Methods:
A survey-based cross-sectional cohort study was performed in pediatric HSCT patients seen at the Dana-Farber Cancer Institute and Boston Children’s Hospital over a 1.5-year period compared with age/sex/Fitzpatrick skin phototype-matched healthy controls. Study participants were surveyed using the validated Glanz survey for pediatric sun protection behavioral research.
Results:
Eighty-five pediatric HSCT patients and 85 controls completed the study. Pediatric HSCT patients more frequently used sunscreen, hats, umbrellas, and sunglasses and obtained full body skin exams compared to controls. No difference was observed in sun exposure during hours of peak sun intensity, frequency of purposeful tanning, tanning bed use, and the number of painful sunburns received between pediatric HSCT patients and controls.
Conclusions:
Although pediatric HSCT patients practice more sun protection behaviors, they experienced harmful sunburns and intentional tanning behaviors at the same rate as their peers. Patient-directed counseling and strategies to improve patient adherence to optimal sun protection behaviors could have a significant impact on the dermatology quality of life in pediatric HSCT patients.
Keywords: pediatric, hematopoietic stem cell transplantation, sun protection, skin cancer, sunburn, tanning, general dermatology, quality improvement, Glanz survey, cross-sectional cohort study
Introduction
Advances in hematopoietic stem cell transplantation (HSCT) have led to improved disease-free survival and reduced morbidity from malignant and nonmalignant conditions. However, HSCT recipients are still at an elevated risk for long-term complications including graft-versus-host disease (GVHD) and skin cancer. While several adjunctive treatments with HSCT such as total body irradiation (TBI), long-term immunosuppression, and voriconazole use are risk factors for skin cancer, sun exposure remains a strong environmental risk factor for skin cancer development in this population.1–3 Therefore, consistent sun avoidance and protection as well as regular dermatologic evaluations are important for HSCT recipients.4 Few studies have examined the sun exposure and protection behaviors specific to pediatric HSCT patients. To address this gap in knowledge, we performed a survey-based cross-sectional cohort study of pediatric HSCT patients and matched controls to assess their sun protection behaviors and skin cancer surveillance practices.
Methods
Pediatric HSCT patients seen at the Dana-Farber Cancer Institute (DFCI) and Boston Children’s Hospital were surveyed over a 1.5-year period (October 2013 to April 2015) under a DFCI IRB-approved protocol (#13–241). All patients and/or legal guardians signed an IRB-approved informed consent. HSCT patients were recruited at routine dermatology clinic visits. Control patients matched by age, sex, and Fitzpatrick skin phototype (FPT) were recruited at routine dermatology and primary care clinic visits. Inclusion criteria included a history of HSCT performed at ≤21 years of age and a timespan between transplantation and study visit of at least one year. Exclusion criteria included HSCT performed at an outside institution and relapse of underlying disease. All study participants underwent full skin examination by a pediatric dermatologist (JTH, EBH). Additional details regarding the inclusion/exclusion criteria, cross-sectional cohort study design, and outcomes on melanocytic nevi, skin cancers, and nonmalignant cutaneous changes were previously reported.4,5
Study participants were asked at their dermatology clinic visits to report average sun exposure, tan-seeking behavior, and sun protection practices over the prior 12 months using a standardized survey (Glanz) validated for pediatric sun protection behavioral research.6
Comparison of continuous variables between HSCT patients and controls were performed with the Wilcoxon rank sum test. Nominal data were compared with Fisher’s exact test. Ordinal/categorical data regarding FPT and sun exposure/protection behaviors were compared with Chi-square linear-by-linear association. P-values less than 0.05 were considered statistically significant. Statistical analyses were performed using SPSS software (Version 25, IBM).
Results
Patient demographic and clinical characteristics are detailed in Table I. The median age of our HSCT cohort at the time of HSCT was 7.4 years (range 0.1–21.0) and 13.8 years (range 1.4–26.1) at the time of study visit/survey administration. The median time from HSCT to the study visit was 3.6 years (range 1.2–16.2). There was no statistical difference in sex, FPT, and patient-reported untanned skin color between HSCT patients and controls. Primary indications for HSCT included 61.2% (52/85) hematologic malignancy, 14.1% (12/85) bone marrow failure, 12.9% (11/85) immunodeficiency, 3.5% (3/85) other malignancy, and 8.2% (7/85) other nonmalignant disease. 36.5% (31/85) of HSCT patients in our study experienced acute or chronic GVHD, 67.1% (57/85) received TBI, and 52.9% (45/85) were exposed to voriconazole which has known photosensitizing effects that could predispose individuals to sunburns and skin cancers.
Table I:
Demographic characteristics of study participants
| Characteristic | HSCT (n = 85) n (%) |
Controls (n = 85) n (%) |
P-value |
|---|---|---|---|
| Median age at transplant; years (range) | 7.4 (0.1–21.0) | - | |
| Median age at study visit; years (range) | 13.8 (1.4–26.1) | 13.7 (1.0–27.3) | 0.72 |
| Median time from HSCT to study visit; years (range) | 3.6 (1.2–16.2) | ||
| Sex | |||
| Male | 53 (62.3) | 53 (62.3) | 1.03 |
| Female | 32 (37.7) | 32 (37.7) | |
| Fitzpatrick skin phototype | |||
| I/II | 49 (57.6) | 47 (55.3) | 0.64 |
| III/IV | 30 (35.3) | 30 (35.3) | |
| V/VI | 6 (7.1) | 8 (9.4) | |
| Color of untanned skin | |||
| Very fair | 16 (18.8) | 12 (14.1) | 0.25 |
| Fair | 43 (50.6) | 36 (42.4) | |
| Olive | 9 (10.6) | 15 (17.6) | |
| Light brown | 12 (14.1) | 19 (22.4) | |
| Dark brown | 4 (4.7) | 3 (3.5) | |
| Very dark | 1 (1.2) | 0 (0.0) | |
| Primary disease | |||
| Hematologic malignancy | 52 (61.2) | - | |
| Bone marrow failure | 12 (14.1) | - | |
| Immunodeficiency | 11 (12.9) | - | |
| Other malignancy | 3 (3.5) | - | |
| Other nonmalignant disease | 7 (8.2) | - | |
| Acute GVHD of the skin | 10 (11.8) | - | |
| Chronic GVHD of the skin | 21 (24.7) | - | |
| Voriconazole use | 45 (52.9) | - | |
| Total body irradiation exposure | 57 (67.1) |
GVHD graft-versus-host disease; P-values are from Chi-square linear-by-linear association unless otherwise specified.
P-value from Wilcoxon rank sum test;
P-value from Fisher’s exact test
21.2% (18/85) of HSCT patients spent at least 3 hours per day outside during peak sun intensity hours (10am-4pm) on weekdays and 36.5% (31/85) of HSCT patients spent at least 3 hours per day outside during peak sun intensity hours on weekends (Table II). No significant differences were observed between HSCT patients and matched controls in practices of intentional sun exposure, including the amount of time spent outside on weekdays and weekends during peak sun intensity hours, frequency of time spent in the sun for the purpose of tanning, and frequency of tanning bed use. No significant difference was observed in the number of sunburns between HSCT patients and controls, with 25.9% (22/85) of HSCT patients reporting one or more red/painful sunburns over the past year compared to 27.1% (23/85) of controls (p=0.87).
Table II:
Comparison of sun exposure and tan-seeking behaviors
| Risk factor | HSCT (n = 85) n (%) |
Controls (n = 85) n (%) |
P-value |
|---|---|---|---|
| Hours outside/day (weekdays 10am-4pm) | |||
| 0–1 hours | 32 (37.6) | 23 (27.0) | 0.18 |
| 1–2 hours | 18 (21.2) | 18 (21.2) | |
| 2–3 hours | 17 (20.0) | 19 (22.4) | |
| 3–4 hours | 8 (9.4) | 14 (16.5) | |
| 4–5 hours | 6 (7.1) | 7 (8.2) | |
| 5–6 hours | 4 (4.7) | 4 (4.7) | |
| Hours outside/day (weekends 10am-4pm) | |||
| 0–1 hours | 20 (23.5) | 14 (16.5) | 0.08 |
| 1–2 hours | 22 (25.9) | 19 (22.4) | |
| 2–3 hours | 12 (14.1) | 12 (14.1) | |
| 3–4 hours | 16 (18.8) | 16 (18.8) | |
| 4–5 hours | 9 (10.6) | 14 (16.5) | |
| 5–6 hours | 6 (7.1) | 10 (11.7) | |
| Number of red/painful sunburns in the past year | |||
| 0 | 63 (74.1) | 62 (72.9) | 0.87 |
| 1 | 15 (17.7) | 15 (17.7) | |
| 2 | 3 (3.5) | 6 (7.0) | |
| 3 | 3 (3.5) | 0 (0.0) | |
| 4 | 0 (0.0) | 0 (0.0) | |
| 5+ | 1 (1.2) | 2 (2.4) | |
| How often do you spend time in the sun withthe purpose of getting a tan? | |||
| Never | 62 (72.9) | 50 (58.8) | 0.11 |
| Rarely | 13 (15.3) | 22 (25.9) | |
| Sometimes | 7 (8.3) | 7 (8.2) | |
| Often | 3 (3.5) | 6 (7.1) | |
| Always | 0 (0.0) | 0 (0.0) | |
| Use of tanning bed | |||
| Yes | 1 (1.2) | 6 (7.1) | 0.123 |
| No | 84 (98.8) | 79 (92.9) | |
P-values are from Chi-square linear-by-linear association unless otherwise specified.
P-value from Fisher’s exact test
Overall, HSCT patients practiced better sun protection behaviors than control patients, endorsing significantly more frequent use of sunscreen, hats, and sunglasses compared to controls (Table III). Furthermore, HSCT patients more frequently stayed in the shade or used an umbrella. However, there was no significant difference in the distribution of HSCT patients who wore shirts with sleeves that covered their shoulders compared to controls.
Table III:
Comparison of sun protection and dermatologic surveillance practices
| Protective factor | HSCT (n = 85) n (%) |
Controls (n = 85) n (%) |
P-value |
|---|---|---|---|
| How often do you wear sunscreen? | |||
| Never | 3 (3.5) | 10 (11.8) | <0.001 |
| Rarely | 4 (4.7) | 12 (14.1) | |
| Sometimes | 9 (10.6) | 24 (28.2) | |
| Often | 18 (21.2) | 14 (16.5) | |
| Always | 51 (60.0) | 25 (29.4) | |
| How often do you wear a hat? | |||
| Never | 4 (4.7) | 18 (21.2) | <0.001 |
| Rarely | 19 (22.3) | 25 (29.4) | |
| Sometimes | 31 (36.5) | 26 (30.6) | |
| Often | 13 (15.3) | 13 (15.3) | |
| Always | 18 (21.2) | 3 (3.5) | |
| How often do you stay in the shade or under an umbrella? | |||
| Never | 2 (2.4) | 7 (8.2) | 0.03 |
| Rarely | 12 (14.1) | 20 (23.5) | |
| Sometimes | 43 (50.6) | 39 (45.9) | |
| Often | 25 (29.4) | 15 (17.7) | |
| Always | 3 (3.5) | 4 (4.7) | |
| How often do you wear a shirt with sleeves that cover your shoulders? | |||
| Never | 2 (2.3) | 3 (3.5) | 0.21 |
| Rarely | 5 (5.9) | 7 (8.3) | |
| Sometimes | 17 (20.0) | 21 (24.7) | |
| Often | 30 (35.3) | 29 (34.1) | |
| Always | 31 (36.5) | 25 (29.4) | |
| How often do you wear sunglasses? | |||
| Never | 11 (12.9) | 22 (25.9) | <0.001 |
| Rarely | 18 (21.2) | 26 (30.6) | |
| Sometimes | 26 (30.6) | 23 (27.1) | |
| Often | 18 (21.2) | 10 (11.7) | |
| Always | 12 (14.1) | 4 (4.7) | |
| Have you ever had your skin checked for skin cancer from head to toe by a health professional? | |||
| Yes | 52 (61.2) | 4 (4.7) | <0.0013 |
| No | 33 (38.8) | 81 (95.3) | |
| Have you or a partner examined your entire body for skin cancer in the past year? | |||
| Yes | 36 (42.4) | 10 (11.8) | <0.0013 |
| No | 49 (57.6) | 75 (88.2) | |
| If yes, how many times? | |||
| 1 | 15 (41.6) | 4 (40.0) | 0.58 |
| 2–6 | 11 (30.6) | 4 (40.0) | |
| 7–12 | 5 (13.9) | 2 (20.0) | |
| 12+ | 5 (13.9) | 0 (0.0) | |
P-values are from Chi-square linear-by-linear association unless otherwise specified.
P-value from Fisher’s exact test
61.2% (52/85) of HSCT patients previously received a full body skin exam (FBSE) from a healthcare professional compared to only 4.7% (4/85) of controls (p<0.001). 42.4% (36/85) of HSCT patients reported self or partner skin examinations within the past year compared to 11.8% (10/85) of controls (p<0.001). Of note, 11.8% (10/85) of HSCT patients underwent self or partner skin examination more than 7 times a year.
Discussion
Our study found no significant differences in sun exposure practices among pediatric HSCT patients compared to matched controls, with more than one-third of HSCT patients spending over 3 hours per day outside during peak sun intensity hours on weekends. In addition, there were no differences in intentional indoor and outdoor tanning practices between groups. Similarly, a prior report of childhood cancer survivors found that 37% did not follow sun protection recommendations.7 While this data may reflect that HSCT patients are not practicing adequate sun avoidance, it may also suggest that these long-term survivors are able to enjoy being outdoors as much as their peers and have a similar desire to have a tanned appearance. While a healthy and active lifestyle should be encouraged for all children, our results emphasize the need for pediatric HSCT survivors to be educated on their increased risk for UV-related skin cancers, counseled on avoidance of intentional tanning, and advised on the importance of sun protection behaviors in an effort to improve long-term outcomes.8
Children exposed to excessive UV radiation have an increased lifetime risk for skin cancers.9,10 UV-related skin damage can be significantly reduced by effective sun protection behaviors including use of sunscreen and sun-protective clothing and avoidance of tanning.11 HSCT patients in our study reported more frequent use of sunscreen, hats, umbrellas, and sunglasses compared to controls, suggesting that some patients and families are aware of this increased risk and are practicing sun protection measures. However, there was no significant difference in number of sunburns experienced by pediatric HSCT patients over the past year compared to controls, with 1 in 4 HSCT patients reporting at least one red or painful sunburn in the past year. These findings suggest that HSCT patients may have an increased tendency to sunburn, or that they are over-reporting sun protection behaviors based on prior counseling and knowledge of expected practices.
A 2015 consensus statement for cancer screening in HSCT patients recommended annual full body skin exam and counseling on skin cancer and sun protection awareness.12 Our study found that pediatric HSCT patients were more likely to have had a FBSE by a healthcare professional and to have performed more self or partner skin examinations compared to controls. However, even at our institution where annual dermatologic evaluation is the standard-of-care, 38.8% (33/85) of HSCT patients had never previously had a FBSE at the time of study enrollment. Routine dermatology visits lead to improved patient education and earlier detection of skin cancer by promoting self-skin exams and timely presentation for evaluation.13,14 In organ transplant recipients, educational interventions and dermatology clinic participation improve sun protection practices and skin cancer awareness.15 Barriers to routine dermatologic care for this population should be further explored and addressed. In addition, while the pediatric patients in this study were not further stratified by age groups, sun exposure and protection behaviors of children could vary with age and the degree of parental/guardian supervision. Future studies aimed at identifying the most vulnerable patient age groups could provide valuable information for targeted sun protection education and awareness programs and help maximize their impact.
Limitations of our study include single-center design, reporter bias, and limited data on patients with darker FPTs. While dermatology evaluations are recommended to all pediatric HSCT patients at our institution, our cohort could be biased for patients with active dermatologic concerns and previous dermatology visits.
The increasing number of hematopoietic stem cell transplants being performed and improved long-term survival of pediatric HSCT patients signifies a growing patient population requiring dermatology care. Our study highlights the need to improve sun protection and avoidance practices in pediatric HSCT patients, a population at higher than average risk for skin cancer and other cutaneous complications. Patient-directed counseling and implementation of strategies designed to increase patient adherence to optimal sun protection behaviors could have a significant positive impact on the dermatologic quality of life of this growing population of transplant survivors.
Funding sources:
This work was supported by a Pilot Project Grant by the Society for Pediatric Dermatology and by a Career Development Award by the Dermatology Foundation. D.E.F. acknowledges grant support from NIH (2R01 AR043369) and the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation.
Footnotes
IRB approval status: Approved by Boston Children’s Hospital IRB; #13-241
Consent for publication: All authors are in agreement with the manuscript contents and consent for publication
Conflict of interest: D.E.F. has a financial interest in Soltego Inc., a company developing SIK inhibitors for topical skin darkening treatments that might be used for a broad set of human applications. The interests of D.E.F. were reviewed and are managed by Massachusetts General Hospital and Partners HealthCare in accordance with their conflict of interest policies.
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