This study included 69 patients whose ages at diagnosis ranged from 3 to 17 years, with a median age of 8 years; 60% of our patients were below the age of 10 years (18.8% were younger than 5 years, and 42.1% were between 5 and 10 years). There are considerable differences in the clinical and pathological features of pediatric HL patients based on geographic region. The average age of diagnosis in the Western world is between 12 and 15 years [5,6,7]. Patients in developing countries tend to present at a younger age. Other studies find comparable ages of diagnosis in developing nations in Africa and Asia, demonstrating a link between HL and infection with the Epstein-Barr virus in these regions [7,8,9].

There were 82.6% male and 17.4% female, resulting in a male-to-female ratio of 4.7:1. Numerous publications [10, 11] have documented male predominance in HL, as did our study, which was comparable to a Pakistan study that revealed a male-to-female ratio of 3.6:1 [8]. The cause for this male dominance should be explored thoroughly. A possible explanation is that gender discrimination is still common in many developing countries. Nodular sclerosis histology was the major pathologic subtype (47.8%), followed by mixed cellularity histology (24.1%), in contrast to other developing countries where mixed cellularity is the prevalent subtype, as described by Faizan et al. [8]. Patients with mixed cellularity and nodular sclerosis had an EFS of 100% and 66%, respectively, with P = 0.005. This was comparable to a previous research in which patients with mixed cellularity histology had a 4-year EFS rate of 95.2%, which was considerably higher than that of patients with nodular sclerosis histology (75.7%; P = 0.008). However, there was no statistical significance regarding OS in our sample [12]. With a threshold of 10 g/dl, the hemoglobin level of all patients was measured. Anemia was detected in 39 individuals (56.5%), which is slightly higher than the 23.1% rate reported by Mondello et al. This may be attributed to the low socioeconomic status and poor nutrition of a significant number of our patients [13]. At diagnosis, 47.8% of our cohort’s patients were in stages I and II, whereas 52.2% were in stages III and IV. Our population has a greater rate of advanced stages compared to others [14]. The difference in our analysis was a more advanced state at presentation, mostly as a result of a delay in diagnosis and referral to pediatric oncologists [5, 8, 15, 16]. In contrast, the majority of newly diagnosed patients in the Western world are in the early stages of disease (stages I–II) [11]. The goal of new therapeutic approaches for pediatric patients with HL is to significantly enhance cure rates while minimizing treatment-related early and late adverse effects. Initial therapeutic approaches for children contain high doses of radiation. In the GPOH-HD 95 research, radiation was only administered to patients who did not achieve complete remission following chemotherapy [17]. Current treatment strategies are based on risk- and response-adjusted therapy, with patients receiving chemotherapy with or without low-dose radiation therapy. Between 1975 and 2010, the 5-year survival rate for pediatric HL improved from 81 to  > 95% [18]. However, in underdeveloped countries, survival is still much lower due to late presentation, inadequate supportive care, and the absence of accessible targeted treatment as salvage therapy, those whose conventional chemotherapy has failed die of disease progression [7, 19].

There are few published studies from Egypt; thus, we undertook the present study to describe outcomes in the Egyptian community, particularly for those treated with response-adapted therapy. Until the end of 2016, all patients in our cohort received combined modality; thereafter, response-based treatment was adopted, and radiation therapy was only administered to patients with SER. The majority of patients in our research were RER patients who attained full remission with PET-CT negative following the second chemotherapy cycle (60 patients). Patients with RER had superior 3-year OS and EFS compared to those with SER (94.7% vs. 74.1%) and (84.8% vs. 74.1%); P = 0.068 and P = 0.351, respectively). These results were consistent with those of Gallamini et al., who reported that the 3-year EFS for RER vs. SER was 95% vs. 82%, respectively, and with those of another study, in which the 3-year EFS was 73.6% vs. 64%, indicating that a positive interim PET has a significant impact on survival [20, 21].

In the present study, CMT (chemotherapy plus radiation) was administered to 22 patients (31.9%), whereas chemotherapy alone was administered to 47 patients (68.1%). The OS and EFS of patients who got CMT were marginally greater than those who did not (95.5% vs. 89.9%) and (87.6% vs. 83.3%), respectively, although these differences were not statistically significant (P = 0.720 and 0.909). This was comparable to a research conducted by Metzger et al. on 86 patients, in which patients who did not undergo irradiation were estimated to have a 5-year EFS of 89.4%, which was comparable to those who did undergo irradiation (87.5%) [22], and in agreement with another randomized research conducted by Jhawar et al., who revealed that 5-year OS was 97.3% for patients receiving CMT and 94.5% for those getting chemotherapy alone (P = 0.001) [23]. In contrast, Ali et al. [9] stated that radiation is the single independent predictor for inferior OS, as determined by multivariate analysis. The 5-year OS and EFS rates for those who had received radiation treatment were 93.4% and 80%, respectively, compared to 30% and 30% for patients who got chemotherapy alone (P < 0.0001) [9, 24]. We found that of the sixty patients who obtained RER despite a negative interim PET, seventeen received combined modality therapy, since CMT was the standard of care regardless of response at that time. The 3-year OS and EFS rates of patients who achieved RER and got CMT were 100% and 88.2%, respectively, compared to 95% and 90% in patients who achieved RER but only received chemotherapy (P = 0.35 for OS and P = 0.71 for EFS). Therefore, radiation can be omitted from RER without compromising treatment outcomes. In the present study, radiation was administered to 22 patients (31.9%), with 15 patients (68.2%) receiving a dosage of 15 Gy and 7 patients (31.8%) receiving a dose of 20 Gy or more. The 3-year OS and EFS of patients who got 15 Gy were (93.3% and 74.3%), respectively, but patients who received 20 Gy or more had a 3-year OS and EFS of 100% and 100%, respectively; however, the P-values were not statistically significant (P = 0.495 & 0.196%). In a different research, the 5-year EFS for patients treated with low-dose radiation treatment (15–25 Gy) was 84%, whereas the 5-year EFS for patients treated with standard dosage (25–35 Gy) was 81%. Consequently, it appears that the outcomes of standard-dose and low-dose radiation are equal; thus, minimizing the dosage to reduce the risk of toxicity should be addressed [25]. Thus, we may apply low-dose radiation without affecting the result while also reducing toxicity. The indication for radiation differs for patients with bulky mediastinal mass; in the COG study AHOD0831, participants with SER or initial bulky areas received radiation, but in the EuroNet-PHL trial, only patients with SER received radiotherapy. In our cohort, there were eight patients with mediastinal enlargement; all of them obtained full remission on interim PET-CT. Three patients had a combined modality, and none experienced relapse; five patients did not get radiation, and only one experienced relapse and attained CR following salvage chemotherapy. Although our sample size was small, we can support the omission of radiotherapy for those with bulky mediastinal mass and achieved RER to avoid late toxicity in the form of cardiotoxicity, pulmonary toxicity, and secondary malignancy, particularly in adolescent females with a higher incidence of breast and thyroid cancer; however, a larger sample size is still required to support our results [26]. As shown in Table 4, the OS and EFS at 3 years for the entire cohort were 91.9% and 83.6%, which is comparable to international studies and more favorable to other developing nations. In the present study, four patients died, with neutropenic sepsis being the cause of death in two patients and illness progression being the cause of death in the other two; effective supportive care is one of the most significant factors in preventing treatment-related mortality.