Proton beam irradiation in pediatric oncology: an overview

The greatest challenge for the treatment of children with cancer is to attain the highest probability of cure with the least morbidity. This has stimulated advances in radiotherapy technology. In recent literature published regarding proton radiation therapy (PRT) for pediatric cancer patients, PRT has been shown to have a distinct advantage over conventional photon therapy because of the ability to confine the high-dose treatment area to the tumor volume and minimize the radiation dose to the surrounding tissue. This is particularly important in children, in whom late effects of radiation to normal tissue can include developmental delay and increased risk of second malignant neoplasms. Several proton facilities are operating world-wide, and several medical centers in the United States and Europe are in the midst of planning and constructing new proton facilities. This may enlarge the role of radiation therapy in the multimodal management of children with cancer.     

A study group on brain tumors in childhood. Introduction, establishment and aims

Tumors of the central nervous system account for 15.7% of all malignancies registered at the documentation center for childhood malignancies in Western Germany. This group constitutes the largest entity of solid tumors. With the exception of medulloblastoma the five-year survival probability of children with cns tumors in only 54%. Prognosis can only be improved by a interdisziplinary and multicentric approach. Recently, the "Gesellschaft für P?diatrische Onkologie (GPO)" has set up a special Brain Tumor Study Group. Members of this group will come from several fields such as neuropediatrics, neurosurgery, radiotherapy, pediatric endocrinology, neuroradiology, neuro-/paidopathology, experimental neurooncology, medical statistics, and pediatric oncology. The major aims are standardization of current strategies for diagnosis and therapy including concepts for early diagnosis, aftercare, and rehabilitation. Moreover, it is planned to develop clinical and experimental research facilities and to establish a brain tumor research data bank.     

Training and education of pediatric radiation oncologists: A survey from the 2019 Pediatric Radiation Oncology Society meeting

To examine the educational background, clinical practice, and preferences regarding continuing medical education (CME) among radiation oncologists who attended the 2019 meeting of the Pediatric Radiation Oncology Society (PROS), a survey consisting of 20 questions was distributed asking for demographic and educational background, clinical practice, and preferences regarding pediatric radiation oncology CME. Of 188 participants, 130 (69.2%) returned the questionnaire. More than 80% reported access to CT simulation, three‐dimensional radiotherapy, and general anesthesia while <30% had access to intraoperative radiotherapy, proton, and heavy particle therapy. After residency, 12.1% did further training in pediatric radiation oncology. When asked about further training in pediatrics after residency, 88.8% answered that there should be a formal training program beyond residency in order to treat children. More than 75% acquired knowledge in pediatric radiation oncology through journals, books, live meetings, and tumor boards. The results of this survey may help Pediatric Radiation Oncology Society (PROS) in creating guidelines and recommendations for improvement in pediatric radiation oncology training and practice support as well as the development of CME activities most likely to benefit practitioners.     

A discourse: the 2002 Wataru W. Sutow lecture. Hodgkin disease in children--perspectives and progress

THE PIONEER: Wataru W. Sutow, 1912-1981, was a remarkable and pivotal leader in pediatric oncology. Early in his medical career, he conducted important clinical and anthropometric studies among Japanese and Marshall Island children exposed to atomic radiation. These studies established standards for childhood growth and development still in use today. Dr. Sutow pioneered the multidisciplinary approach to childhood cancer by combining multidrug chemotherapy protocols with surgery and radiotherapy in the common childhood solid tumors. The textbook "Clinical Pediatric Oncology," of which he was the senior editor, served to define the discipline of pediatric oncology and educate a new era of oncologists in the curative treatment for childhood cancer. THE PAST AND PRESENT: The first edition of "Clinical Pediatric Oncology," published in 1973, demonstrated that only children with early-stage localized Hodgkin disease had a realistic opportunity for cure. Soon the use of combined-modality therapy consisting of low-dose, involved-field radiation plus multi-agent chemotherapy emerged, and made the goal of cure realistic for all patients. This approach is now universal. Today, the 5-year relative survival rate for American children with Hodgkin disease, who are under 14 years of age, is 94%, a dramatic and remarkable achievement. FUTURE: Management of children with Hodgkin disease now involves clinical staging and risk-adapted, combined-modality therapy. Clinical and translational research initiatives that hold promise for children with Hodgkin disease in the future include: use of the WHO Classification System combining morphologic and biologic criteria; noninvasive staging procedures with increased sensitivity and specificity; development of a useful prognostic index to define groups for risk-adapted therapy; high-dose therapy with stem cell transplantation; and novel therapies.     

Children's Oncology Group's 2013 blueprint for research: Radiation oncology

Radiation therapy (RT) is used to treat children with CNS tumors, solid tumors or Hodgkin lymphoma. Pediatric radiation oncologists have provided critical input into the development and implementation of concepts for clinical trials to further define the modality's role and test newer methods to reduce side effects or intensify therapy. The quality of pediatric oncology clinical trials that include radiation therapy is linked to the quality of guidelines. Radiation oncology is an adult medical specialty; thus, pediatric radiation oncologists are uniquely positioned to work with adult cancer investigators in the reorganized US National Cancer Institute Clinic Trials Network. Pediatr Blood Cancer 2013; 60: 1037–1043. © 2012 Wiley Periodicals, Inc.     

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??Radiation therapy??RT?? is used to treat children with CNS tumors??solid tumors or Hodgkin lymphoma??including TBI. Pediatric radiation oncologists have provided critical input into the development and implementation of concepts for clinical trials to further define the modality’s role and test newer methods to reduce side effects or intensify therapy. The quality of pediatric oncology clinical trials that include radiation therapy is linked to the quality of guidelines. Radiation oncology is an adult medical specialty??thus??pediatric radiation oncologists are uniquely positioned to work with adult cancer investigators.     

Ability of hospitals to care for pediatric emergency patients.

CONTEXT: The needs of children in emergency situations differ from those of adults and require special attention, yet there has been no study of the ability of U.S. hospitals to care for emergently or critically ill children. OBJECTIVE: To estimate the distribution of pediatric services available at U.S. hospitals with emergency departments (EDs). DESIGN: Self-report survey of 101 hospital EDs. PARTICIPANTS: Stratified probability sample of all U.S. hospitals operating EDs. RESULTS: The majority of hospitals that usually admit pediatric patients do not have separate pediatric facilities. Hospitals without a pediatric department, ward, or trauma service usually transfer critically injured pediatric trauma patients; however, nearly 10% of hospitals without pediatric intensive care facilities admit critically injured children to their own facilities. Likewise, 7% of hospitals routinely admit pediatric patients known to require intensive care to their adult intensive care units rather than transferring the patient to a facility with pediatric intensive care facilities. Few hospitals have protocols for obtaining pediatric consultation on pediatric emergencies. Appropriately sized equipment for successful care of infants and children in an emergency situation was more likely to be missing than adult-sized equipment, and significant numbers of hospitals did not have adequate equipment to care for newborn emergencies. CONCLUSION: Emergent and critical care of infants and children may not be well integrated and regionalized within our health care system, suggesting that there is room for improvement in the quality of care for children encountering emergent illness and trauma.     

Register for the evaluation of side effects after radiation in childhood and adolescence--first results

BACKGROUND: Late effects after radiotherapy in childhood and adolescence have mainly been characterized retrospectively with small patient numbers. Therefore the German Group of Pediatric Radiation Oncology (APRO) established the "RegIster for the evaluation of late Side effects after radiation in childhood and adolescence" (RiSK). After a pilot phase starting in 2001 documentation has been performed all over Germany since 2004. This analysis shows the first results of "RiSK". PATIENTS AND METHODS: Radiation parameters including detailed organ doses as well as toxicity evaluations were collected prospectively from centers all over Germany in the study center. Standardized documentation forms were used. Documentation is planned for all children who receive radiotherapy in one of the German pediatric therapy trials. RESULTS: Until December 31st 2006, 696 documentations of radiotherapy and 526 acute as well as 836 late follow-up documentation forms have been collected. Altogether, 41 patients with late grade 3 and 16 patients with late grade 4-side effects were identified. Side effects mainly concerned joints with functional impairment (after combined radiotherapy and surgery), the bowel, skin and subcutis as well as blood parameters under continued chemotherapy. Patients with late side effects of a higher grade were mainly treated for Ewing's or soft tissue sarcomas (n=235 patients), representing 33.8% of all patients in this study. CONCLUSION: Fortunately, up to now only a few late grade 3 or 4 side effects of radiotherapy are shown for almost 700 documented patients. For further results, especially for the characterization of dose-effect-relationships, this study has to be continued with a higher patient number and a longer follow-up.     

Daily subcutaneous amifostine administration during irradiation of pediatric head and neck cancers

Five pediatric patients with head and neck cancers were treated with radiotherapy. Subcutaneous injections of 200 mg flat dose amifostine were given 30 min prior to radiation fractions. A total of 129 amifostine injections were done. Grade 3 nausea occurred three times and emesis only once. Hypotension, hypocalcemia, or allergic reactions following injections were not recorded. No grade 3 or 4 mucosal or skin reactions occurred. After 16 months, all patients were alive and disease-free. There were no grade 3 or 4 side effects of radiotherapy on follow-up. Further studies with more patients are required to determine the role of amifostine in pediatric radiation oncology, but these data should contribute to the clinical spectrum of amifostine use in pediatric oncology.     

Requirements and performance profile of the Paediatric Radiation Oncology Working Group (APRO): evaluation of the present situation and description of future developments

BACKGROUND: Radiation therapy is an integral component in the management of childhood malignancies and undergoes a continuous process of optimization within the prospective trials of the GPOH. At present there are approximately 20 active protocols, some specifying radio-oncological study questions, in which about 500 to 600 children annually are given radiotherapy. MATERIALS/METHODS: The Pediatric Radiation Oncology Working Group (APRO) of the German Society for Radiation Oncology (DEGRO) represents the organizational link between GPOH and DEGRO. Their activities range from phrasing guidelines of radio-oncological therapy, through writing a protocol for a prospective study on radiation-induced late effects (RISK--in co-operation with GPOH, 695 patients registered so far) and organizing meetings for information transfer, to implementing radio-oncology within the prospective studies of the GPOH by establishing study chairs for radio-oncology when radio-oncological questions are a primary focus and/or to function as a reference institution for quality assurance. These activities also include individual case consultations outside the study proper. Twice annually the members of the APRO meet for an update on current knowledge and future directions where a representative of the GPOH is invited to contribute special aspects of pediatric oncology. CONCLUSIONS: In the future, modern technology (intensity modulated radiotherapy, proton therapy, inclusion of imaging in treatment planning) will be part of disease management in pediatric oncology. A working group for modern radiotherapy technology was established to enhance this development. Prospective studies of the GPOH with primary or secondary radio-oncological questions require the implementation of corresponding tasks (documentation, monitoring, etc.) in order to meet future demands on clinical trials and to achieve the aims of the protocol. Consequently adequate financial support is indispensable.     

Complementary and alternative therapies in pediatric oncology

Evidence on the science of complementary and alternative medicine (CAM) in children with cancer is slowly evolving. Most parents of children with cancer want their children to receive state-of-the-art therapy, which generally includes chemotherapy, radiation, and surgery. Increasingly, they also want the concomitant use of CAM therapies to help effect a cure or to alleviate symptoms. The ideal model of integrative pediatric oncology offers safe and effective CAM therapies in a pediatric hospital or medical center setting which participates in the clinical trials network of a pediatric oncology cooperative group setting.     

Pediatric oncology situation analysis (Jordan)

This article highlights the current situation of pediatric oncology in Jordan by reviewing the available population based data from the surveillance. Cancer among children aged less than 15 years make up 4 to 6% of all registered new cancer cases in all ages each year. The major types of cancer in females for the year 2008 are leukemia 32.2%, central nervous system 18.8%, skeletal and soft tissue 8.8%, lymphomas 5.5%, and sympathetic 5.5%, whereas in males, they are leukemia 28.1%, central nervous system 18.8%, lymphomas 16.2%, skeletal and soft tissue 7% and sympathetic 6.3%. Children with cancer receive treatment through pediatric oncology wards in King Hussein Cancer Center (KHCC) and Royal Medical Services hospital or through pediatric departments in King Abdullah university Hospital and Princes Rahma hospital with full government coverage of the treatment expenses. Currently the pediatric palliative care program is limited to KHCC which provides inpatient care, and out-patients and drop-in care on a daily basis to provide symptom management, counseling, and other services as appropriate. The lack of palliative care in other hospital and pediatric home care coverage stress the need to develop special plan of action to initiate these services.     

Growth impairment after ifosfamide-induced nephrotoxicity in children

BACKGROUND: The goal of this study was to analyze long-term consequences of ifosfamide-induced nephrotoxicity on growth and renal function in children treated for cancer. PROCEDURE: In a retrospective study, departments for pediatric oncology and nephrology in Germany, Austria, and Switzerland were asked to report patients with serious long-term nephrotoxicity after ifosfamide-treatment. Data at first appearance of renal dysfunction and at the last renal examination were collected using a standardized questionnaire. RESULTS: Fifty-nine patients with tubulopathy (35 severe, 24 moderate) following ifosfamide therapy were eligible for analysis of long-term outcome (median follow-up 4 years, range 1.1 to 12.9). Median height standard deviation score was significantly reduced at renal diagnosis, and at last renal examination (-1.7 and -2.1 respectively, P < 0.01 at each point in time). Patients with tubulopathy also had stunted growth in comparison with a control group of cancer patients without renal disease (mean difference at last examination: 7.3 cm (95% confidence interval: 2.5 to 12.1 cm). In patients with severe tubulopathy, glomerular filtration rate deteriorated significantly over time. End-stage renal disease was reported in one patient only, not solely caused by ifosfamide. CONCLUSION: Depending on the extent of tubular dysfunction, patients with ifosfamide-induced nephrotoxicity experienced significant growth impairment and a slow decline in glomerular filtration rate.     

Benign outcome of RSV infection in children with cancer

BACKGROUND: High case-fatality rates have been reported among adults who develop respiratory syncytial virus (RSV) infection while being treated for oncologic diseases, particularly after bone marrow transplantation. Previous reports of RSV infection among children with primary and acquired immunodeficiencies describe increased morbidity compared with that seen in immunocompetent children, but there have been few reports describing the outcome of RSV infection specifically among pediatric oncology patients. METHODS: We retrospectively reviewed the charts of all children being treated by the Pediatric Oncology Service at Memorial Sloan-Kettering Cancer Center who had positive tests for RSV between the Fall of 1994 and the Spring of 1998. Patients on the BMT Service were excluded from this analysis. RESULTS: Eighteen RSV infections were identified among pediatric oncology patients, who were being treated with aggressive, predominantly alkylator-based chemotherapy for a variety of oncologic diagnoses. Nine episodes of RSV infection (50%) were treated with specific antiviral therapy. Only one death less than 100 days from the diagnosis of RSV infection occurred among these 18 patients and was attributed to progressive leukemia. The remaining patients recovered fully, although three were readmitted with respiratory symptoms within two weeks of discharge. Seven patients had concurrent infection with other pathogenic organisms. CONCLUSIONS: In striking contrast with the outcome of RSV infection in adult oncology patients, there may be low mortality associated with RSV infection in pediatric oncology patients. It is possible that scheduled anti-neoplastic therapy need not be delayed for these patients when the diagnosis of RSV infection is made.     

Radiation-sensitive genetically susceptible pediatric sub-populations

Major advances in pediatric cancer treatment have resulted in substantial improvements in survival. However, concern has emerged about the late effects of cancer therapy, especially radiation-related second cancers. Studies of childhood cancer patients with inherited cancer syndromes can provide insights into the interaction between radiation and genetic susceptibility to multiple cancers. Children with retinoblastoma (Rb), neurofibromatosis type 1 (NF1), Li-Fraumeni syndrome (LFS), and nevoid basal cell carcinoma syndrome (NBCCS) are at substantial risk of developing radiation-related second and third cancers. A radiation dose-response for bone and soft-tissue sarcomas has been observed in hereditary Rb patients, with many of these cancers occurring in the radiation field. Studies of NF1 patients irradiated for optic pathway gliomas have reported increased risks of developing another cancer associated with radiotherapy. High relative risks for second and third cancers were observed for a cohort of 200 LFS family members, especially children, possibly related to radiotherapy. Children with NBCCS are very sensitive to radiation and develop multiple basal cell cancers in irradiated areas. Clinicians following these patients should be aware of their increased genetic susceptibility to multiple primary malignancies enhanced by sensitivity to ionizing radiation.     

Patterns of Failure for Pediatric Glioblastoma Multiforme Following Radiation Therapy

Despite aggressive multimodal therapy for pediatric glioblastoma multiforme (GBM), patient survival remains poor. This retrospective review of patients with GBM aims to evaluate the patterns of failure after radiation therapy (RT). The study included 14 pediatric patients treated with RT at the Children's Hospital of Philadelphia from 2007 to 2015. With a median follow‐up of 16.9 months, 13 (92.9%) developed recurrent disease. Of recurrences, nine (69.2%) were in‐field, three (23.1%) were marginal, and one (7.7%) was distant. The majority of patients treated with adjuvant radiation failed in the region of high‐dose RT, indicating the need for improvements in local therapy.     

PEDIATRIC HEMATOLOGY AND ONCOLOGY IN IRAN

Pediatric hematology and oncology (PHO) is a rapidly expanding field. It has been our goal to meet the needs and increasing demands for comprehensive medical care of children suffering from chronic blood diseases and malignancies. In the past decade we have been able expand and optimize the PHO services throughout Iran, in general and in respect to their prevalence and clinical importance, by trained pediatric hematologist-oncologists, pediatric surgeons and improved para clinical facilities. Major beta-thalassemics receive blood transfusion and chelation therapy according to the current standards mostly at regional blood banks centers. To curb major beta-thalassemia a premarital screening program has been enacted and abortion has been legitimized if major thalassemia is diagnosed by CVS. Hemophiliacs are supervised and treated as indicated by Iranian Hemophilia Comprehensive Care Centers (IHCCC). Screening for transfusion related complications and transmitted viral diseases (HBV, HCV and HIV) in both cohorts are carried out in regular intervals and necessary management will be then carried out as indicated at respective specialized units. Childhood malignancies are treated according to protocols adopted from accredited institutions in the USA and Europe, with almost comparable results. BMT is available for selected patients with beta-thalassemia or malignancies. By going to public we have been able to rise general awareness about chronic blood diseases and childhood malignancies and have initiated establishment of parents groups and formation of NGOs to support these children and their families. Foundation of Iranian Society of Pediatric Hamatology and Oncology (ISPHO) in the year 2000 has been another step forward to consolidate and coordinate the available manpower and facilities.

Conclusion: By evaluation of the country's main problems and shortcomings and conduction of collaborative studies and operation planning one will succeed to get the expected feedback and scientifically based approach to provide medical services to far reaching underdeveloped regions.     

Pseudotumoral diseases: ten years of experience in a pediatric oncology department]

PURPOSE: Among the 350 new patients per year treated in the pediatric oncology department of the Gustave-Roussy Institute, about 2% have no tumor. This study analyzes these children presenting a pseudotumoral disease. PATIENTS AND METHODS: Ten-year-retrospective study. Patients for which no follow up in oncology was necessary after one consultation or hospitalization were selected. OUTCOME: Between 1990 and 2000, 64 patients were seen in the pediatric department for pseudotumoral disease. The reasons of orientation were mainly a soft tissue mass (15 cases), an abdominal mass (14 cases), or a bone lesion (13 cases). Diagnosis was most often infectious diseases (33 cases), or post-traumatic lesions (10 cases). Diagnosis was established following several consultations or an hospitalization for 29 of 64 patients. In 75% of the cases new investigations were necessary to determine the diagnosis. A biopsy was performed in 19. For two children, diagnosis was corrected after the beginning of chemotherapy. CONCLUSION: Pseudotumoral diseases leading to a consultation in pediatric oncology are rare and represent two per cent of the patients. For these difficult cases, only a pluridisciplinary discussion may lead to diagnosis.     

Management of retinoblastoma with radiation

OBJECTIVE: To evaluate the role of radiation therapy in the management of retinoblastoma. DESIGN: Retrospective analysis. METHOD: From January 1993 to March 1994, one hundred and eleven children (150 eyes) of retinoblastoma were referred for radiotherapy. The diagnosis was based on clinical examination and ocular ultrasonogram for both the eyes. The radiation treatment policy involved 40 Gy in 20 fractions over 4 weeks delivered with sedation for children under 1 year of age, 36 Gy in 9 fractions over 3 weeks under ketamine anesthesia for 1-4 years of age and for >4 years of age, a dose of 50 Gy in 25 fractions over 5 weeks. The initial tumor regression was evaluated by A and B mode ultrasonography and/or CT scan. RESULTS: The age distribution ranged from two months to six years (median - 20 months). Bilaterality was observed in 39 out of 111 cases (35%). The male to female ratio was 1.8:1. Eighty two of the 111 children were treated by definitive external beam radiation to one or both eyes. Fifteen cases received adjuvant radiotherapy after enucleation, and 14 had extensive disease for which palliative radiotherapy was offered. We observed a complete response in 54% of cases, partial response in 32%, and none in 14% of cases. Forty per cent (40%) eye survival was documented at the end of 28 months. The complication rate encountered was about 15%. CONCLUSION: Radiotherapy is an effective modality of treatment in significant number of patients with retinoblastoma. However, it requires appropriate fractionation, precise colimation and careful immobilization with general anesthesia.