Late effects of childhood cancer treatment in long-term survivors diagnosed before the age of 3 years - A multicenter, nationwide study.

BACKGROUND: The effect of age on the incidence of late sequelae that occur after anticancer treatment in childhood is still not fully elucidated. In this multicenter study of long-term survivors diagnosed before age of three, we investigated the prevalence of late effects many years after treatment. METHODS: The study group (n = 561) was selected from the Polish National Childhood Cancer Survivors Registry (n = 1761) created in 2007. A survivor was defined as an individual who has survived at least 5 years after completion of anticancer treatment. All children were diagnosed between 1991 and 2016, mean age at diagnosis was 1.82 years (range 0.03-2.99) and median follow up time - 9.85 years (range 5.0-23.6). They were treated in accordance with international protocols approved by the Polish Pediatric Leukemia and Lymphoma Group and Polish Solid Tumor Group. Chemotherapy alone was used in 192 (34.2%), chemotherapy and radiotherapy - 56 (10%), chemotherapy and surgery - 176 (31.4%), chemotherapy, radiotherapy, and surgery - 79 (14.1%), and surgery alone in 58 patients (10.3%). RESULTS: Of all patients enrolled to the study, only 94 (16.8%) had normal function of all organs. Seventy-six (13.5%) children developed dysfunction in one organ, another 83 (14.8%) had symptoms or complaints suggestive of dysfunction in two organs or systems, 88 (15.7%) had abnormalities in three organs, and 220 (39.2%) had at least four or more dysfunctions. In the entire study group, dysfunctions most frequently (> 20% of cases) involved the following organs/systems: circulatory - 21.8%, urinary - 30.8%, gastrointestinal - 20.8%, immune - 23.5%, vision - 20.7%, hearing - 21.8%, and oral and masticatory dysfunction - 26.9%. We did not find any significant differences in organ dysfunction between children diagnosed under the age of 1 and those diagnosed at the age of 1-3, except for a lower incidence of thyroid abnormalities (p = 0.007) and the higher prevalence of liver dysfunction in youngest patients. In the subset with longer follow-up period (> 10 years) more frequent thyroid abnormalities (p = 0.019), male (p = 0.002) and female (p = 0.026) gonads dysfunction, as well as musculoskeletal problems (p < 0.001) were observed. Among subjects who received radiotherapy compared to those who did not, short stature (p = 0.001), and dysfunction of the following systems/organs - circulatory (p = 0.049), urinary (p = 0.012), thyroid gland (p < 0.0001), nervous (p = 0.007), immunological (p = 0.002), liver (p = 0.03), dental or chewing difficulties (p = 0.001), hearing (p = 0.001) and musculoskeletal (p = 0.026) were more frequently reported. When multimodal therapy was applied (chemotherapy, radiotherapy, and surgery) a higher incidence of short stature (p = 0.007), urinary system disorders (p < 0.0001), thyroid dysfunction (p < 0.0001), hearing loss (p < 0.0001), and skin problems (p = 0.031) were observed. CONCLUSION: This study confirms that radiotherapy and some specific toxicity of cytostatics are the most important factors affecting organ function. Apart from a higher incidence of liver dysfunction in the youngest patients, there were no significant differences in organ and system toxicities between children diagnosed under the age of 1 and those diagnosed at the age of 1-3. We have shown that this group requires systematic, careful and long-term follow-up.

Double Endoprosthesis in the Management of Refractory Metastatic Primary Bone Tumors in Children and Young Adults.

BACKGROUND: Although not all children can be cured yet, much more emphasis is placed on the quality of life during and after cancer treatment. In the case of recurrence, mutilating treatment is still the prevalent option. In our study, we explored the role of limb salvage surgery for young patients with metastatic malignant bone tumors after endoprosthesis reconstruction during the first line of treatment and evaluated the impact of the local control modality in disease control and functional outcomes. MATERIALS AND METHODS: Eleven patients with bone tumor treated between 2007 and 2018 were included in this study. Both during primary treatment and during recurrence, limb salvage surgery was performed using a modular or expandable custom-made replacement system. Peri- and postoperative care for both surgeries were similar. All patients were given chemotherapy before and after both surgeries, according to the oncological guidelines. RESULTS: Seven patients (63.6%) are alive with a median follow-up of 6.5 years from diagnosis. None had local recurrence. Five-year estimates of event-free survival and overall survival were 36.27% and 79.55%, respectively. Median time between the first and second surgery was 2.7 years. Three patients presented with postoperative complications following both surgeries and required resurgical intervention. Three months following the second surgery, the Musculoskeletal Tumor Society Scale (MSTS) scores were 15-27 points (21 points on average-60%). CONCLUSIONS: Limb salvage surgery is feasible and offers good chance of cure with a reasonable rate of complications and good function in patients with recurrent bone sarcoma after endoprosthesis reconstruction during the first line of treatment.

Distal Tibial Reconstruction in the Management of Primary Bone Tumors in Children and Adolescents.

BACKGROUND: Distal tibial primary bone tumors are rare, and options for limb salvage surgery are limited and challenging. Importantly, local control has shown to be crucial and necessary for cure, and radical surgery is one of the most important components of therapy for some bone sarcomas. We investigated the feasibility and functional and oncological outcomes of distal tibial reconstruction using endoprosthesis in children with malignant bone tumors. METHODS: Fourteen patients (median age 13.6 years) with primary bone tumors (4 Ewing sarcoma [ES], 10 osteosarcoma) of the distal tibiae were treated during 2013-2019. All patients had reconstruction using a modular (13 patients) or expandable custom-made titanium bone replacement system (1 patient). All patients received chemotherapy before and after surgery. RESULTS: Twelve patients (85.7%) are alive with a median follow-up 20 months from diagnosis. Five-year estimates of event-free survival and overall survival were 60.6% and 76.4%, respectively. Three patients had postoperative complications requiring second surgery. Maximum dorsiflexion and plantar flexion of the foot were 20 degrees (range 0-20 degrees) and 20 degrees (range 5-20 degrees), respectively. CONCLUSION: For select distal tibial sarcomas, after neoadjuvant chemotherapy pretreatment and radical resection, reconstruction using an endoprosthesis as a radical surgery provides an option was associated with a low rate of short-term local complications and relatively good early function. LEVEL OF EVIDENCE: Level IV, therapeutic study.