Outcome of Children and Adolescents With Primary Intracranial Germinoma Treated With Chemotherapy and Reduced Dose-Field Irradiation: A Prospective Brazilian Experience.

PURPOSE: This prospective Brazilian single-arm trial was conducted to determine response to chemotherapy and survival after response-based radiotherapy in children with intracranial germinomas, in the setting of a multi-institutional study in a middle-income country (MIC) with significant disparity of subspecialty care. PATIENTS AND METHODS: Since 2013, 58 patients with histologic and/or serum and CSF tumor marker evaluations of primary intracranial germ cell tumors were diagnosed; 43 were germinoma with HCGß levels ≤200 mIU/mL and five between 100 and 200 mIU/mL. The treatment plan consisted of four cycles of carboplatin and etoposide followed by 18 Gy whole-ventricular field irradiation (WVFI) and primary site(s) boost up to 30 Gy; 24 Gy craniospinal was prescribed for disseminated disease. RESULTS: Mean age 13.2 years (range, 4.7-25.5 years); 29 were males. Diagnosis was made by tumor markers (n = 6), surgery (n = 25), or both (n = 10). Two bifocal cases with negative tumor markers were treated as germinoma. Primary tumor location was pineal (n = 18), suprasellar (n = 14), bifocal (n = 10), and basal ganglia/thalamus (n = 1). Fourteen had ventricular/spinal spread documented by imaging studies. Second-look surgery occurred in three patients after chemotherapy. Thirty-five patients achieved complete responses after chemotherapy, and eight showed residual teratoma/scar. Toxicity was mostly grade 3/4 neutropenia/thrombocytopenia during chemotherapy. At a median follow-up of 44.5 months, overall and event-free survivals were 100%. CONCLUSION: The treatment is tolerable, and WVFI dose reduction to 18 Gy preserves efficacy; we have demonstrated the feasibility of successfully conducting a prospective multicenter trial in a large MIC despite resource disparity.

Photodynamic therapy to control oral candidiasis in a pediatric patient undergoing head and neck radiotherapy.

Candida albicans is an opportunistic yeast of the oral microbiome which can cause candidiasis in systemically susceptible individuals, such as those undergoing cancer treatment. The local management of the oral lesions is challenging and may be significantly improved with photodynamic therapy (PDT). PDT consists of an association of light with a photosensitizing agent and oxygen, whose interaction produces reactive oxygen species capable of reducing non-specific microbial contamination without causing side effects. This study aimed to report a case in which oral candidiasis was managed with PDT. A 12-year-old male patient undergoing head and neck radiotherapy (HNRT) for Undifferentiated Mesenchymal Neoplasm presented with dysgeusia, oral pain, and yeast infection on the 13th session of HNRT. The patient used topical antifungals for 30 consecutive days with no lesion or symptom remission. PDT was then proposed and the lesion was healed after a single PDT session, with no further clinical signs of infection and return to normal oral function. Local and non-invasive management of oral candidiasis is of utmost importance for immunocompromised patients, with good acceptability, no systemic side effects, and no drug interactions.

High-grade gliomas in children and adolescents: is there a role for reoperation?

OBJECTIVE: Tumors of the CNS are the main causes of childhood cancer and have an incidence that exceeds that of leukemia. In addition, they are the leading causes of cancer-related death in childhood. High-grade gliomas account for 11% of such neoplasms and are characterized by aggressive clinical behavior and high morbidity and mortality. There is a lack of studies focusing on the factors that can prolong survival in these patients or guide therapeutic interventions. The authors aimed to investigate the factors related to longer survival durations, with a focus on reoperation for gross-total resection (GTR). METHODS: In this retrospective cohort study, the authors analyzed 78 patients diagnosed with high-grade gliomas occurring across all CNS locations except diffuse intrinsic pontine gliomas. Patients 0 to < 19 years of age were followed up at the Pediatric Oncology Institute. Overall survival (OS) and progression-free survival (PFS) were analyzed in the context of various prognostic factors, such as age, sex, histology, extent of tumor resection, reoperation for GTR, adjuvant treatment, and treatment initiation from 2010 onward. RESULTS: With a mean age at diagnosis of 8.7 years, 50% of the patients were female and approximately 39% underwent GTR at some point, which was already achieved in approximately 46% of them in the first surgery. The median OS was 17 months, and PFS was 10 months. In terms of median OS, the authors found no significant difference between those with reoperation for GTR and patients without GTR during treatment. Significant differences were observed in the OS in terms of the extent of resection in the first surgery, age, sex, Ki-67 expression, adjuvant treatment, and treatment initiation from 2010 onward. Furthermore, the PFS values significantly differed between those with GTR in the first surgery and Ki-67 expression ≥ 50%. CONCLUSIONS: This study demonstrates the importance of GTR for these neoplasms, highlights the role of surgeons in its achievement in the first attempt, and questions the role of reoperation for this purpose. Finally, this study further supports the use of combined adjuvant treatment for the improvement of OS and PFS.

Kidney-sparing whole abdominal irradiation in Wilms tumor: Potential advantages of VMAT technique.

PURPOSE: To present a preliminary clinical experience and a dosimetric comparison of kidney-sparing volumetric modulated arc therapy (VMAT) with three-dimensional conformal radiotherapy (3D-CRT) for whole abdominal irradiation (WAI), in the setting of Wilms tumor (WT) treatment. MATERIALS AND METHODS: From a total of 20 consecutive WT cases treated with adjuvant irradiation, seven were submitted to WAI with VMAT. Renal function and survival rates were evaluated, and, for comparison purposes, similar VMAT and 3D-CRT treatment plans were performed for WAI patients, and differences were dosimetrically evaluated regarding doses to the remaining kidney and other organs at risk and the planning target volume (PTV). RESULTS: After a median follow-up time of 40.8 months (35.3-52.2), no acute significant intestinal toxicity was observed, and median creatinine clearance was 110.1 and 103.3 mL/min/1.73 m², respectively, before treatment and at last follow-up for WAI patients (P = 0.128). For comparative plans, maximum and median doses were lower for the remaining kidney with VMAT than with 3D-CRT. VMAT was associated with better PTV coverage as compared with 3D-CRT, with superior results for all the evaluated parameters (D95, D2, V100%, V98%, V95%; P = 0.018). CONCLUSION: The use of VMAT technique is associated with lower radiation doses to the remaining kidney and better coverage to the PTV than 3D-CRT technique for WAI, with preliminary clinical experience showing a favorable toxicity profile. Long-term results from prospective studies might prove the ability of VMAT to spare renal function in the setting of WT treatment.

Clinical practice and outcomes of palliative radiation therapy in pediatric oncology patients: An international comparison of experiences from two distinct countries and health care systems.

BACKGROUND AND PURPOSE: This study describes clinical outcomes of palliative radiation therapy (RT) for children treated in distinct health-care environments-the US where there is advanced integration of palliative resources and Brazil, a country in the process of developing provisions for pediatric palliative care. METHODS AND MATERIALS: Palliative RT cases of pediatric oncology patients aged ≤21-years from 2010 to 2016 in two Brazil-based and one US-based (Johns Hopkins Hospital, JHH) academic centers were reviewed in this study. RESULTS: Eighty-eight pediatric patients were treated to 131 lesions with palliative RT. Forty-nine patients from the JHH cohort comprised 84 cases and 39 patients from the Brazil cohort comprised 46 cases. The most common indication for palliative RT was pain (55% overall, 39% Brazil, 63% JHH). Sixty-seven percent of patients experienced a complete (CR) or partial response (PR) to palliative RT, 12% reported stable symptoms (SS), and 22% reported progressive symptoms (PS). The median survival from the end of palliative RT was 3.6 months (95% confidence interval (CI), 2.3-4.8 months). When treated with palliative RT for pain, 83% of patients experience CR/PR, facilitating reduction or discontinuation of opiates in 46% of these patients. CONCLUSION: Despite different practices, the clinical results using palliative RT for pediatric patients treated in two unique healthcare environments demonstrated it is an effective tool for pediatric oncology patients across systems.

Reirradiation for Recurrent Pediatric Central Nervous System Malignancies: A Multi-institutional Review.

PURPOSE: Reirradiation has been proposed as an effective modality for recurrent central nervous system (CNS) malignancies in adults. We evaluated the toxicity and outcomes of CNS reirradiation in pediatric patients. METHODS AND MATERIALS: The data from pediatric patients <21 years of age at the initial diagnosis who developed a recurrent CNS malignancy that received repeat radiation therapy (RT) across 5 facilities in an international pediatric research consortium were retrospectively reviewed. RESULTS: Sixty-seven pediatric patients underwent CNS reirradiation. The primary diagnoses included medulloblastoma/primitive neuroectodermal tumor (n=20; 30%), ependymoma (n=19; 28%), germ cell tumor (n=8; 12%), high-grade glioma (n=9; 13%), low-grade glioma (n=5; 7%), and other (n=6; 9%). The median age at the first course of RT was 8.5 years (range 0.5-19.5) and was 12.3 years (range 3.3-30.2) at reirradiation. The median interval between RT courses was 2.0 years (range 0.3-16.5). The median radiation dose and fractionation in equivalent 2-Gy fractions was 63.7 Gy (range 27.6-74.8) for initial RT and 53.1 Gy (range 18.6-70.1) for repeat RT. The relapse location was infield in 52 patients (78%) and surrounding the initial RT field in 15 patients (22%). Thirty-seven patients (58%) underwent gross or subtotal resection at recurrence. The techniques used for reirradiation were intensity modulated RT (n=46), 3-dimensional conformal RT (n=9), stereotactic radiosurgery (n=4; 12-13 Gy × 1 or 5 Gy × 5), protons (n=4), combined modality (n=3), 2-dimensional RT (n=1), and brachytherapy (n=1). Radiation necrosis was detected in 2 patients after the first RT course and 1 additional patient after reirradiation. Six patients (9%) developed secondary neoplasms after initial RT (1 hematologic, 5 intracranial). One patient developed a secondary neoplasm identified shortly after repeat RT. The median overall survival after completion of repeat RT was 12.8 months for the entire cohort and 20.5 and 8.4 months for patients with recurrent ependymoma and medulloblastoma after reirradiation, respectively. CONCLUSIONS: CNS reirradiation in pediatric patients could be a reasonable treatment option, with moderate survival noted after repeat RT. However, prospective data characterizing the rates of local control and toxicity are needed.

Practice patterns of palliative radiation therapy in pediatric oncology patients in an international pediatric research consortium.

BACKGROUND/OBJECTIVES: The practice of palliative radiation therapy (RT) is based on extrapolation from adult literature. We evaluated patterns of pediatric palliative RT to describe regimens used to identify opportunity for future pediatric-specific clinical trials. DESIGN/METHODS: Six international institutions with pediatric expertise completed a 122-item survey evaluating patterns of palliative RT for patients ≤21 years old from 2010 to 2015. Two institutions use proton RT. Palliative RT was defined as treatment with the goal of symptom control or prevention of immediate life-threatening progression. RESULTS: Of 3,225 pediatric patients, 365 (11%) were treated with palliative intent to a total of 427 disease sites. Anesthesia was required in 10% of patients. Treatment was delivered to metastatic disease in 54% of patients. Histologies included neuroblastoma (30%), osteosarcoma (18%), leukemia/lymphoma (12%), rhabdomyosarcoma (12%), medulloblastoma/ependymoma (12%), Ewing sarcoma (8%), and other (8%). Indications included pain (43%), intracranial symptoms (23%), respiratory compromise (14%), cord compression (8%), and abdominal distention (6%). Sites included nonspine bone (35%), brain (16% primary tumors, 6% metastases), abdomen/pelvis (15%), spine (12%), head/neck (9%), and lung/mediastinum (5%). Re-irradiation comprised 16% of cases. Techniques employed three-dimensional conformal RT (41%), intensity-modulated RT (23%), conventional RT (26%), stereotactic body RT (6%), protons (1%), electrons (1%), and other (2%). The most common physician-reported barrier to consideration of palliative RT was the concern about treatment toxicity (83%). CONCLUSION: There is significant diversity of practice in pediatric palliative RT. Combined with ongoing research characterizing treatment response and toxicity, these data will inform the design of forthcoming clinical trials to establish effective regimens and minimize treatment toxicity for this patient population.