Discussion
The actual burden of childhood cancer in lower middle income countries is unknown due to lack of population-based cancer registries. According to GLOBOCAN’s 2020 estimates, South-central Asia and Eastern Asia have the highest incidence of cancers in children (<19 years) with over 143,000 new cases annually. The exact incidence and prevalence of pediatric cancer cases in low and middle-income countries like Pakistan are unknown due to a lack of resources needed to establish and maintain a centralized national cancer registry; however, it is estimated that around 8000 new pediatric cancer cases and diagnosed in Pakistan each year accounting for almost 10% of the total reported cancer cases in the country.[4] Overall survival of childhood cancer patients has improved fairly over the last few decades, from less than 30% to about 80% in high-income countries owing to the introduction of aggressive multimodal treatment protocols which include a combination of chemotherapy, radiation, and surgery.[5] However, the overall survival is much lower in Pakistan and other low and middle-income countries due to a number of intrinsic hurdles negatively affecting outcomes such as poor nutrition, lack of capital to build and maintain proper facilities and train personnel as well as a lack of infrastructure to gain access to healthcare. Radiation therapy is a critical component of childhood cancer worldwide yet access, in terms of equipment as well as geographic location, is limited in LMICs like Pakistan where only few hospitals are treating pediatric cancer patients in the entire country and only our institute utilizes general anesthesia for planning and treatment of pediatric patients.[6] The availability of expert manpower for pediatric radiation therapy remains limited.
The Surveillance, Epidemiology, and End Results (SEER) registry of the National Cancer Institute reported a decline in the use of RT for ALL, NHL, and retinoblastoma from 1973 to 2008 as new prognostic groupings lead to treatment with surgery alone or intensified chemotherapy for certain patients instead of RT. However, the use of RT for neuroblastoma, Wilms tumor, brain and bone cancer has declined slightly over the years, but remained proportionately stable for AML, Hodgkin’s lymphoma and soft tissue cancers.[7-9] Trends observed in our data showed an increase in RT use for bone tumors, soft tissue tumors, and Wilms tumor and a decrease in ALL patients as shown in Figure 3.
Improving pediatric oncology care can be achieved by determining the actual burden of childhood cancer so that specific demands will be put on the management of childhood cancer in an environment with limited resources. The number of patients receiving RT at our institution has increased steadily over the years, almost doubling over the 10-year period, possibly reflecting the collaboration with pediatric oncologist resulting in patient’s referral to radiotherapy and increase in incidence of cancer cases as well as improvement in prompt identification and treatment of such patients.
For safe and effective delivery of radiation, patients’ immobility for 15-20 minutes is required which can be difficult for children especially in an unfamiliar environment of the radiation suite without parents or caregivers around. Hence, anesthesia is routinely used for patients under the age of 3, and sedation requirements decrease with increasing age. Anesthesia use carries a major risk for complications including ‘failure to rescue’ from cardiopulmonary collapse, respiratory depression or airway obstruction, or the need for emergent procedures like intubation. However, we did not have any such adverse event reported for our patients. Also, the long-term effects of repeated GA on neurocognition are unknown and is a question for future research in our region.[10] Equipment and drugs to safely deliver anesthesia are costly and require a dedicated medical team including anesthesiologists, pediatric nurses, and respiratory therapists.[11] A recent analysis reported better tolerability of daily RT without anesthesia with the use of AVATAR (Audiovisual-Assisted Therapeutic Ambience in Radiation Therapy) during RT delivery. This unique approach has potential to minimize the burden of health care staff and health care cost needed in LMIC.[12]
Advances in multimodal therapy for childhood cancer have led to more than 80% cure and survival rates for pediatric solid tumors but the adverse effects of therapy may cause debilitating events and sometimes poor quality of life beyond the primary disease process. The Childhood Cancer Survivor Study (CCSS) estimated that 1 in 5 childhood cancer survivors died after 30 years of survivorship with 1 in 10 deaths due to treatment-related factors.[13] Radiotherapy-related late effects include cardiac dysfunction, cognitive deficits, hypopituitarism, cataracts, ototoxicity, spinal and bone growth abnormalities, pulmonary fibrosis, bowel fibrosis, etc. A noteworthy point for pediatric cancers remain the long term radiation induced effects which may adversely impact the quality of life among childhood cancer survivors. These late effects might be compromised neurocognitive functions, memory loss, cataract formations, endocrine problems, bone weakness, and other primary tumors. Subsequent neoplasms due to radiation exposure are the major cause of no relapse-related mortality with the CCSS reporting a 20.5% 30-year cumulative incidence. Hence, it is important to screen and monitor childhood survivors for late toxicity according to standard guidelines and deliver a lower cumulative dose for fewer treatment-related side effects. Our study reported different aspects of radiation practices including age at treatment, body site(s) affected, and radiation delivery with time has a potential to work on survivorship issues of children treated with RT. This guides us on planning survivorship program for these children tailored according to the common body sites irradiated.
The World Health Organization’s Global Initiative for Childhood Cancer goal to reach 60% survival rate for pediatric cancer by 2030 can only be done with a special focus on cancer care in LMICs. This includes establishing specialized pediatric RT units to alleviate the burden on existing facilities. For a sustainable system, suitable equipment including pediatric-specific immobilization devices, anesthesia machines, etc. should be acquired, and adequate, trained staff including radiation oncologists, clinical medical physicists, radiation therapy technologists, and technical machine engineers should be hired.[14] Staffing ratio and competency can improve over time to build capacity in terms of patient numbers and RT techniques. Exchange of ideas between experts at different institutions at combined forums such as tumor board meetings, etc. could also help develop appropriate treatment protocols for the maximum benefit of the patients. Clinical research and studies on RT practices from LMIC are needed for the development of new treatment strategies in children with cancer specifically applicable to our region who do not enroll in clinical trials. To overcome the challenges faced by LMIC, sharing our radiotherapy experience will help in collaboration, and assistance from international organizations, societies, and institutions to make an appreciable difference.