Late Effects of Chemoradiotherapy in Pediatric Hodgkin’s Disease

Gözdaşoĝlu, Sevgi; Çavdar, Ayhan O.; Babacan, Emel; Mengübaş, K; Yavuz, Gülsan; Ünal, Emel; Pamir, Ali; Öçal, Gönül; Haluk, I.; Gökçora, I. Haluk

doi:10.1179/joc.1995.7.5.463

Cited by 7 publications

(7 citation statements)

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“…Common late complications of childhood cancers after treatment include neurological, cardiac, pulmonary and gonadal disorders, reduction in bone mass, defective bone and soft tissue development, and increased susceptibility to secondary malignant tumors (1,2,3,4,5,6,7,8,9). Hyperthyroidism including Graves’ disease, thyroiditis, hypothyroidism, thyroid nodules and thyroid cancers are the most commonly encountered thyroid gland disorders that are known to be related with radiotherapy (6,10,11,12,13). The objective of this study was to evaluate thyroid function in pediatric Hodgkin’s lymphoma patients in complete remission with chemotherapy and radiotherapy.…”

Section: Introductionmentioning

confidence: 99%

Thyroid Functions in Long-Term Survivors of Pediatric Hodgkin’s Lymphoma Treated with Chemotherapy and Radiotherapy - Original Article

Demirkaya

Sevinir²,

Sağlam³

et al. 2011

jcrpe

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Objective: Post-treatment endocrine disturbances are common in cancer patients who have received radiotherapy or chemotherapy. The objective of this study was to evaluate the thyroid functions of long-term survivors of pediatric Hodgkin’s lymphoma treated with chemotherapy and radiotherapy.Methods: Thyroid functions of 55 Hodgkin’s lymphoma patients (M/F:2.05/1) in complete remission were evaluated retrospectively.Results: The mean age of the patients at diagnosis was 10.35±4.09 (range: 2.83-17) years and the mean follow-up period was 5.54±3.68 (range: 0.92-13.92) years. All patients received chemotherapy; a total of 50 patients (90.9%) underwent radiotherapy, 42 (76.4%) of whom received neck/mantle radiotherapy. Thyroid function tests were abnormal in 14 (24.5%) patients and normal - in the remaining 41 (74.5%). A diagnosis of subclinical and overt hypothyroidism was made in 11 (78.6%) and 3 (21.4%) patients with abnormal thyroid function tests, respectively. Nearly one-fourth (21.4%) of all thyroid function disorders were detected in the first year of follow-up. A statistically significant correlation was found between the dose of mantle radiotherapy and thyroid function disorder (p=0.002). In addition, statistically significant correlations were established between thyroid examination or thyroid ultrasonography findings and thyroid functions (p <0.001 or p=0.006, respectively).Conclusions: Radiation-induced thyroid disorders may develop in pediatric Hodgkin’s lymphoma patients in complete remission starting as early as the first year after treatment and are dose-dependent. Patients, particularly those who have been exposed to radiotherapy of the neck, must be followed up closely for occurrence of thyroid dysfunctions.Conflict of interest:None declared.

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Section: Introductionmentioning

confidence: 99%

Thyroid Functions in Long-Term Survivors of Pediatric Hodgkin’s Lymphoma Treated with Chemotherapy and Radiotherapy - Original Article

Demirkaya

Sevinir²,

Sağlam³

et al. 2011

jcrpe

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“…S1 . Most studies reported that the majority of HL survivors developed or maintained normal and regular menstrual cycles (median percentage of HL survivors with regular cycle 100%, range 79–100%, nine studies; 168 patients) ( Horning et al , 1981 ; Whitehead et al , 1982 ; Andrieu and Ochoa-Molina, 1983 ; Perrone et al , 1989 ; Hudson et al , 1993 ; Gözdasoglu et al , 1995 ; Madsen et al , 1995 ; Donaldson et al , 2007 ; Zaletel et al , 2010 ). Hudson et al (1993) mentioned that three patients developed amenorrhea during therapy but resumed spontaneous menses 2–4 years after completion of therapy.…”

Section: Resultsmentioning

confidence: 99%

Reproductive ability in survivors of childhood, adolescent, and young adult Hodgkin lymphoma: a review

Drechsel

Pilon

Stoutjesdijk

et al. 2023

Human Reproduction Update

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BACKGROUND Owing to a growing number of young and adolescent Hodgkin lymphoma (HL) survivors, awareness of (long-term) adverse effects of anticancer treatment increases. The risk of impaired reproductive ability is of great concern given its impact on quality of life. There is currently no review available on fertility after childhood HL treatment. OBJECTIVE AND RATIONALE The aim of this narrative review was to summarize existing literature on different aspects of reproductive function in male and female childhood, adolescent, and young adult HL survivors. SEARCH METHODS PubMed and EMBASE were searched for articles evaluating fertility in both male and female HL survivors aged <25 years at diagnosis. In females, anti-Müllerian hormone (AMH), antral follicle count, premature ovarian insufficiency (POI), acute ovarian failure, menstrual cycle, FSH, and pregnancy/live births were evaluated. In males, semen-analysis, serum FSH, inhibin B, LH, testosterone, and reports on pregnancy/live births were included. There was profound heterogeneity among studies and a lack of control groups; therefore, no meta-analyses could be performed. Results were presented descriptively and the quality of studies was not assessed individually. OUTCOMES After screening, 75 articles reporting on reproductive markers in childhood or adolescent HL survivors were included. Forty-one papers reported on 5057 female HL survivors. The incidence of POI was 6–34% (median 9%; seven studies). Signs of diminished ovarian reserve or impaired ovarian function were frequently seen (low AMH 55–59%; median 57%; two studies. elevated FSH 17–100%; median 53%; seven studies). Most survivors had regular menstrual cycles. Fifty-one studies assessed fertility in 1903 male HL survivors. Post-treatment azoospermia was highly prevalent (33–100%; median 75%; 29 studies). Long-term follow-up data were limited, but reports on recovery of semen up to 12 years post-treatment exist. FSH levels were often elevated with low inhibin B (elevated FSH 0–100%; median 51.5%; 26 studies. low inhibin B 19–50%; median 45%; three studies). LH and testosterone levels were less evidently affected (elevated LH 0–57%, median 17%; 21 studies and low testosterone 0–43%; median 6%; 15 studies). In both sexes, impaired reproductive ability was associated with a higher dose of cumulative chemotherapeutic agents and pelvic radiotherapy. The presence of abnormal markers before treatment indicated that the disease itself may also negatively affect reproductive function (Females: AMH<p10 9%; one study and Males: azoospermia 0–50%; median 10%; six studies). Reports on chance to achieve pregnancy during survivorship are reassuring, although studies had their limitations and the results are difficult to evaluate. In the end, a diminished ovarian reserve does not exclude the chance of a live birth, and males with aberrant markers may still be able to conceive. WIDER IMPLICATIONS This review substantiates the negative effect of HL treatment on gonadal function and therefore young HL survivors should be counseled regarding their future reproductive life, and fertility preservation should be considered. The current level of evidence is insufficient and additional trials on the effects of HL and (current) treatment regimens on reproductive function are needed. In this review, we make a recommendation on reproductive markers that could be assessed and the timing of (repeated) measurements.

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“…These rates are very similar to pregnancy outcomes in the general population (Gnoth et al 2003 ; Wang et al 2003 ; Wesselink et al 2017 ). Most previous (cohort)studies mentioned number of female HL survivors achieving pregnancy or a live birth during follow up, without evaluating their wish to conceive, time to conceive or other fertility-related factors that may affect their reproductive potential (Beek et al 2007 ; Drechsel et al 2023 ; Fernandez-Pineda et al 2018 ; Gözdasoglu et al 1995 ; Green and Hall 1988 ; Horning et al 1981 ; Licht et al 2021 ; Mackie et al 1996 ; Madsen et al 1995 ; McCullough et al 2010 ; Papadakis et al 1999 ; Perrone et al 1989 ; Reulen et al 2009 ; Swerdlow et al 1996 ; Sy Ortin et al 1990 ; van der Kaaij et al 2012 ; Wilimas et al 1980 ). Among the two studies who specifically assessed pregnancy rates in females attempting pregnancy after diagnosis, reported pregnancy rates were comparable to our observations (77% of 26 survivors and 81% of 218 studied survivors, respectively) (Horning et al 1981 ; van der Kaaij et al 2012 ).…”

Section: Discussionmentioning

confidence: 99%

Clinical and self-reported markers of reproductive function in female survivors of childhood Hodgkin lymphoma

Drechsel

Broer

Stoutjesdijk

et al. 2023

J Cancer Res Clin Oncol

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Purpose To evaluate the impact of treatment for Hodgkin lymphoma (HL) on clinical reproductive markers and pregnancy outcomes. Methods This study was embedded within the DCOG LATER-VEVO study; a Dutch, multicenter, retrospective cohort study between 2004 and 2014. Serum anti-Müllerian hormone (AMH), follicle stimulating hormone (FSH), inhibin B, antral follicle count (AFC), and self-reported (first) pregnancy outcomes were evaluated in female childhood HL survivors and controls. Results 84 HL survivors and 798 controls were included, aged 29.6 and 32.7 years old at time of assessment. Median age at HL diagnosis was 13.4 years. Cyclophosphamide equivalent dose (CED-score) exceeded 6000 mg/m2 in 56 women and 14 survivors received pelvic irradiation. All clinical markers were significantly deteriorated in survivors (odds-ratio for low AMH (< p10) 10.1 [95% CI 4.9; 20.6]; low AFC (< p10) 4.6 [95% CI 2.1; 9.9]; elevated FSH (> 10 IU/l) 15.3 [95% CI 5.7; 41.1], low Inhibin B (< 20 ng/l) 3.6 [ 95% CI 1.7; 7.7], p < 0.001). Pregnancy outcomes were comparable between survivors and controls (± 80% live birth, ± 20% miscarriage). However, survivors were significantly younger at first pregnancy (27.0 years vs 29.0 years, P = 0.04). Adjusted odds-ratio for time to pregnancy > 12 months was 2.5 [95% CI 1.1; 5.6] in survivors, p = 0.031. Adverse outcomes were specifically present after treatment with procarbazine and higher CED-score. Conclusion HL survivors appear to have an impaired ovarian reserve. However, chance to achieve pregnancy seems reassuring at a young age. Additional follow-up studies are needed to assess fertile life span and reproductive potential of HL survivors, in particular for current HL treatments that are hypothesized to be less gonadotoxic.

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Late Effects of Chemoradiotherapy in Pediatric Hodgkin’s Disease

Cited by 7 publications

References 6 publications

Thyroid Functions in Long-Term Survivors of Pediatric Hodgkin’s Lymphoma Treated with Chemotherapy and Radiotherapy - Original Article

Thyroid Functions in Long-Term Survivors of Pediatric Hodgkin’s Lymphoma Treated with Chemotherapy and Radiotherapy - Original Article

Reproductive ability in survivors of childhood, adolescent, and young adult Hodgkin lymphoma: a review

Clinical and self-reported markers of reproductive function in female survivors of childhood Hodgkin lymphoma

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