Hodgkin lymphoma (HL) accounts for 18% of annual cancer diagnoses in children and young adults (AYA)[15]. Today, five-year event-free survival (EFS) and overall survival (OS) in HL exceed 85% and 95%, respectively[16]. This success is attributed largely to the expanded use of risk-based, multimodal therapy (chemotherapy + radiotherapy [R.T.]) and sequential therapeutic trials to continuously refine the standard of care. Despite overall progress, population-based studies report worse outcomes in adolescents compared to other age groups. Furthermore, survivors of childhood and adolescent classical HL are at high risk for secondary cancers, infertility, and cardiovascular disease later in their life after successful chemoradiotherapy combination treatment[17, 18]. Therefore, it is necessary to plan the treatment strategy reasonably, understand the prognostic risk factors of cohort among children and young adulthood, and classify high-risk groups accordingly to help clinicians effectively evaluate survival and make treatment decisions.
We collected 13,854 children and young adulthood with HL from the SEER database. The results showed that the cancer-specific survival rate of young adulthood aged 26–34 years with HL was significantly higher than that of aged 2–14 years. This study found seven independent risk factors through univariate and multivariate Cox regression models, including age, sex, stage, the number of first primary cancer, chemotherapy, and histological type (Mixed cellularity and Lymphocyte-depleted). The nomogram includes these factors to establish a predictive model to predict the 3-, 5-, and 10-year CSS of children and young adulthood with HL. We first use a nomogram to predict and validate CSS in childhood and young adulthood HL. This nomogram has good accuracy and reliability and is of great significance to clinical patients. Previous studies have found prognostic factors for HL[19–21]. However, no study has used these influencing factors to construct a prediction model for CSS prediction of children and young adulthood with HL. Although the influencing factors we identified have previously been shown to be independent risk factors, we integrated these risk factors to construct a nomogram predicting long-term CSS in children and young adulthood with HL.
Previous studies have shown that various prognostic factors (age, gender, B-symptoms, erythrocyte sedimentation rate and number of affected lymph node areas) will affect the patient’s survival[22, 23]. Our study found that age is an independent risk factor for HL in children and young adulthood, and the survival rate of older young adulthood is lower, the same as previous research results. Justine M Kahn et al[24]. found that patients aged ≥ 15 years had worse event-free survival (EFS) and overall survival (OS) than younger patients, and they identified that the magnitude of the effect of age on EFS differed by histology, which may also be a reason. These findings support the hypothesis that classical Hodgkin lymphoma in adolescents may be biologically distinct from similar histopathologic entities in children[25]. In addition, treatment of HL, especially in children and young adulthood, is still an important issue. With the widespread development of neoadjuvant chemotherapy and radiation therapy, the survival rate of patients with HL has improved significantly[26, 27]. With an increasing cure rate, people begin to centre their concerns around the treatment-associated toxicity[28]. How to balance the benefit and risks of treatments is a critical problem. In our study, we found that patients who underwent chemotherapy had a higher risk of death than those who did not underwent chemotherapy. On the contrary, patients who underwent radiation therapy had a higher survival rate than those who did not underwent radiation therapy; this is consistent with the results of a previous study[29]. However, previous study results show that event-free survival (EFS) rates favor patients receiving radiotherapy by up to 10%[30, 31]. This may be because all major children and several adult in HL research groups have followed a response-based treatment adaptation and toxicity-saving model over the past thirty years by reducing or eliminating RT. and adjusting chemotherapy[30]. In clinical practice, research shows that high-dose chemotherapy can achieve high therapeutic effects, RT has also been improved and reduced in HL patients' treatment plans, thereby eliminating radiation in certain subgroups of patients[32].
In addition, we found that the vast majority of cases (9,470 [70.0%]) presented as nodular sclerosis (NS) variant (i.e., expansile lymphoid nodules surrounded by thick bands of sclerosis); this is similar to previous research[25]. The vast majority of cases belong to the NS variant and grading into NS1 (grade 1), NS2s (sarcomatous/syncytial variant), and NS2f (grade 2 (fibrohistiocytic variant)) is likely of prognostic relevance[33]. Furthermore, only high eosinophilic counts and NS2 histology were associated with a worse prognosis. However, the multivariate COX regression analysis we used showed that NS had no statistically significant impact on prognosis, while children and young adults in HL with lymphocyte depletion had a 5-year specific survival rate of approximately 68.4%, similar to previous research results[34]. This result reported that the 5-year progression-free survival and overall survival rate of patients with lymphocyte depletion are significantly lower than those of patients with other subtypes of classical Hodgkin lymphoma. Approximately 28% of cases are diagnosed in patients between the ages of 18–39, 64% of patients have advanced disease (stage III-IV).
However, our research still has certain limitations. First, because our study is a retrospective case study based on the SEER database, some possible variables such as dose of radiotherapy and chemotherapy, genetic factors, tumor recurrence, Etc., are unavailable. However, we have included essential variables such as histology subtypes, tumor stage, and other vital elements that determine the prognosis and will not cause devastating deviations. Second, we included patients from 1975 to 2020. With the improvement of treatment methods, the cancer-specific survival rate of patients in different years should be different. Finally, all the data used in our study were downloaded from the SEER database, and the constructed nomogram lacks external data to validate. Therefore, it is necessary to use external validation further to test the accuracy and reliability of the prediction model. Next, we will conduct further prospective studies in our hospital to externally validate the accuracy of this prediction model and further promote the clinical application.