Long-Term Toxicities among Wilms Tumor Survivors

Successive trials conducted by the National Wilms Tumor Study have resulted in very high cure rates for children with Wilms tumor (WT). These trials have also significantly reduced the indications for doxorubicin and higher doses of RT in WT. Late toxicities after multimodality treatment especially RT, continues to be a major problem among WT survivors. Higher doses of RT is the most important factor responsible for the many late effects including congestive heart failure, secondary malignant neoplasms, hypogonadism, infertility and pregnancy complications, pulmonary disease, musculoskeletal effects, renal failure and diabetes mellitus. The potential for novel RT techniques like IMRT and proton therapy to reduce the incidence of these toxicities is discussed. The surveillance recommendations for WT survivors are mainly derived from the COG long-term follow-up guidelines. The future directions in late effects research include novel research to improve current knowledge of association between RT doses to target organs and late effects, discovery of novel biomarkers, and identification of predictive genetic biomarkers. Despite all these advances, there are significant challenges facing the global health care community that need to be overcome before the benefits of these innovations in late effects research can be translated to individual cancer survivors

Cochlear implantation after radiation therapy for acoustic neuroma.

Neurofibromatosis type 2 (NF-2) represents the complex issue of hearing restoration after treatment for a patient with bilateral acoustic neuromas. This scenario is difficult for skull base teams considering that all treatment options (including observation of tumors) pose a risk to the patient for further or total hearing loss. In this case of a patient with bilateral deafness, restoration options were auditory brainstem or cochlear implantation (CI). The deciding factor for CI was based on the presence of a functioning cochlear nerve and blood supply. Ultimately, treatment with radiation therapy and subsequent CI proved effective as evidenced by dramatic improvement in communication (with lip reading cues) and speech perception on 1-year audiologic testing. Radiosurgery followed by CI may represent a potential emerging option for patients with NF-2

Harmonica consensus, controversies, and future directions in radiotherapy for pediatric Wilms tumors

Radiotherapy (RT) is essential for multimodality treatment of pediatric renal tumors, particularly in higher-risk and metastatic disease. Despite decades of use, particularly for Wilms tumor, there remain controversies regarding RT indications, timing, dose, and targets. To align global management, we address these issues in this international HARMONIsation and CollAboration (HARMONICA) project. There are multiple knowledge gaps and opportunities for future research including: (1) utilization of advanced RT technologies, including intensity-modulated RT, proton beam therapy, combined with image-guided RT to reduce target volumes; (2) impact of molecular biomarkers including loss of heterozygosity at 1p, 16q, and 1q gain on RT indications; (3) mitigation of reproductive toxicity following RT; (4) promotion of RT late effects research; and (5) support to overcome challenges in RT utilization in low- and middle-income countries where 90% of the world's children reside. Here, we outline current status and future directions for RT in pediatric renal tumors

Complete Response of a Patient With a Mismatch Repair Deficient Aggressive Pituitary Adenoma to Immune Checkpoint Inhibitor Therapy: A Case Report

BACKGROUND AND IMPORTANCE: Aggressive pituitary adenomas (APAs) are pituitary tumors that are refractory to standard treatments and carry a poor prognosis. Current treatment guidelines are not standardized but combine surgical resection, radiation therapy, and chemotherapy. Temozolomide is the only chemotherapeutic agent with documented effectiveness and is recommended for APA in European Society of Endocrinology clinical guidelines. CLINICAL PRESENTATION: A 57-year-old man presented with visual deterioration and bitemporal hemianopsia. MRI of the brain demonstrated a sellar mass suspected to be pituitary macroadenoma with displacement of the stalk and optic nerve impingement. The patient underwent stereotactic endoscopic transsphenoidal resection of the mass. Postoperative MRI demonstrated gross total resection. Pathology revealed a sparsely granulated corticotroph adenoma with malignant transformation. Immunohistochemistry showed loss of expression of MLH1 and PMS2 in the tumor cells. Proton therapy was recommended given an elevated Ki67 index and p53 positivity. Before radiotherapy, there was no radiographic evidence of residual tumor. Temozolomide therapy was initiated after surveillance MRI showed recurrence at 16 months postoperatively. However, MRI demonstrated marked progression after 3 cycles. Next-generation sequencing using the MSK-IMPACT platform identified somatic mutations in MLH1 Y548lfs*9 and TP53 R337C . Immunotherapy with ipilimumab/nivolumab was initiated, and MRI demonstrated no residual tumor burden 34 months postoperatively. CONCLUSION: APA is a tumor with frequent recurrence and a short median expected length of survival. Here, we demonstrate the utility of immunotherapy in a single case report of APA, with complete resolution of recurrent APA and improved survival compared with life expectancy

Io’s Optical Aurorae in Jupiter’s Shadow

Decline and recovery timescales surrounding eclipse are indicative of the controlling physical processes in Io’s atmosphere. Recent studies have established that the majority of Io’s molecular atmosphere, SO _2 and SO, condenses during its passage through Jupiter’s shadow. The eclipse response of Io’s atomic atmosphere is less certain, having been characterized solely by ultraviolet aurorae. Here we explore the response of optical aurorae for the first time. We find oxygen to be indifferent to the changing illumination, with [O i ] brightness merely tracking the plasma density at Io’s position in the torus. In shadow, line ratios confirm sparse SO _2 coverage relative to O, since their collisions would otherwise quench the emission. Io’s sodium aurora mostly disappears in eclipse and e-folding timescales, for decline and recovery differ sharply: ∼10 minutes at ingress and nearly 2 hr at egress. Only ion chemistry can produce such a disparity; Io’s molecular ionosphere is weaker at egress due to rapid recombination. Interruption of a NaCl ^+ photochemical pathway best explains Na behavior surrounding eclipse, implying that the role of electron impact ionization is minor relative to photons. Auroral emission is also evident from potassium, confirming K as the major source of far red emissions seen with spacecraft imaging at Jupiter. In all cases, direct electron impact on atomic gas is sufficient to explain the brightness without invoking significant dissociative excitation of molecules. Surprisingly, the nonresponse of O and rapid depletion of Na is opposite the temporal behavior of their SO _2 and NaCl parent molecules during Io’s eclipse phase

Proton therapy for pediatric malignancies: Fact, figures and costs. A joint consensus statement from the pediatric subcommittee of PTCOG, PROS and EPTN

Radiotherapy plays an important role in the management of childhood cancer, with the primary aim of achieving the highest likelihood of cure with the lowest risk of radiation-induced morbidity. Proton therapy (PT) provides an undisputable advantage by reducing the radiation 'bath' dose delivered to non-target structures/volume while optimally covering the tumor with tumoricidal dose. This treatment modality comes, however, with an additional costs compared to conventional radiotherapy that could put substantial financial pressure to the health care systems with societal implications. In this review we assess the data available to the oncology community of PT delivered to children with cancer, discuss on the urgency to develop high-quality data. Additionally, we look at the advantage of combining systemic agents with protons and look at the cost-effectiveness data published so far. (C) 2018 Elsevier B.V. All rights reserved