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A letter to the editor is presented regarding a study of the ancillary-beam technique for planning gradient-shaped field-junction in pencil beam scanning proton therapy.

Proton beam therapy (PBT) is an effective pediatric brain tumor treatment. However, the resulting microstructural changes within and around irradiated tumors are unknown. We retrospectively applied diffusion tensor imaging (DTI) and free-water imaging (FWI) on diffusion-weighted magnetic resonance imaging (dMRI) data to monitor microstructural changes during the PBT and after 8 months in a pilocytic astrocytoma (PA) and normal-appearing white matter (NAWM). We evaluated the conventional MRI- and dMRI-derived indices from six MRI sessions (t0–t5) in a Caucasian child with a hypothalamic PA: at baseline (t0), during the PBT (t1–t4) and after 8 months (t5). The tumor voxels were classified as "solid" or "fluid" based on the FWI. While the tumor volume remained stable during the PBT, the dMRI analyses identified two different response patterns: (i) an increase in fluid content and diffusivity with anisotropy reductions in the solid voxels at t1, followed by (ii) smaller variations in fluid content but higher anisotropy in the solid voxels at t2–t4. At follow-up (t5), the tumor volume, fluid content, and diffusivity in the solid voxels increased. The NAWM showed dose-dependent microstructural changes. The use of the dMRI and FWI showed complex dynamic microstructural changes in the irradiated mass during the PBT and at follow-up, opening new avenues in our understanding of radiation-induced pathophysiologic mechanisms in tumors and the surrounding tissues. [ABSTRACT FROM AUTHOR]

• Fourteen mediastinal lymphoma patients treated by pencil beam scanning proton therapy. • Deep inspiration breath-hold by active breathing coordinator to reduce patient motion. • Robust intensity modulated proton therapy with focused objectives. • Voxel-wise robustness evaluation at the interface between lungs and cardiac tissues. To comprehensively describe the treatment of mediastinal lymphoma by pencil beam scanning (PBS) proton therapy. Fourteen patients underwent PBS proton treatment in a supine position in deep inspiration breath-hold (DIBH). Three DIBH computed tomography (CT) scans were acquired for each patient to delineate the Internal Target Volume (ITV). Intensity-modulated proton therapy (IMPT) was planned by min–max robust optimization on the ITV, with a 6 mm setup and 3.5% range uncertainties. Robustness analysis was performed and dose coverage was visually inspected on the corresponding voxel-wise minimum map. Layer repainting was set equal to 5 to compensate for cardiac motion. Intra-fraction reproducibility during treatment was assessed by repeated daily DIBH X-ray imaging. Finally, an additional CT was acquired at half treatment to estimate the impact of inter-fraction dosimetric reproducibility. IMPT guaranteed robust mediastinal target coverage and organs-at-risk sparing. However, visual voxel-wise robustness evaluation showed that in five patients a second optimization with focused objectives in the cost-function was necessary to achieve a robust coverage of the target regions at the interface between lungs and soft tissue. In six patients, repainting was not used due to excessive treatment time length and poor patient compliance. Intra-fraction average reproducibility was within 1 mm/1degree. On repeated CT scans, inter-fraction setup errors and/or anatomical changes showed minimal dosimetric differences in CTV coverage. IMPT in DIBH is effective and reproducible to treat mediastinal lymphomas. Caution is recommended to guarantee robust dose delivery to high-risk regions at the interface between lungs and soft tissue. [ABSTRACT FROM AUTHOR]

Poster Highlights: Poster highlights 11 CL: CNS PH-0357: Proton therapy re-irradiation of intracranial meningiomas failing after previous radiation therapy. D. Amelio, D. Scartoni, S. Vennarini, A. Turkaj, I. Giacomelli, M. Amichetti. [Extracted from the article]

Background and purpose Proton therapy is the emerging treatment modality for craniospinal irradiation (CSI) in pediatric patients. Herein, special methods adopted for CSI at proton Therapy Center of Trento by pencil beam scanning (PBS) are comprehensively described. Materials and methods Twelve pediatric patients were treated by proton PBS using two/three isocenters. Special methods refer to: (i) patient positioning in supine position on immobilization devices crossed by the beams; (ii) planning field-junctions via the ancillary-beam technique; (iii) achieving lens-sparing by three-beams whole-brain-irradiation; (iv) applying a movable-snout and beam-splitting technique to reduce the lateral penumbra. Patient-specific quality assurance (QA) program was performed using two-dimensional ion chamber array and γ-analysis. Daily kilovoltage alignment was performed. Results PBS allowed to obtain optimal target coverage (mean D98% > 98%) with reduced dose to organs-at-risk. Lens sparing was obtained (mean D1 ∼ 730 cGyE). Reducing lateral penumbra decreased the dose to the kidneys (mean Dmean < 600 cGyE). After kilovoltage alignment, potential dose deviations in the upper and lower junctions were small (average 0.8% and 1.2% respectively). Due to imperfect modeling of range shifter, QA showed better agreements between measurements and calculations at depths >4 cm (mean γ > 95%) than at depths < 4 cm. Conclusions The reported methods allowed to effectively perform proton PBS CSI. [ABSTRACT FROM AUTHOR]

Abstract: Biologic activities of IL-16 have been well described (e.g., chemotaxis of CD4+ cells, CD25 upregulation, secretion of IL-1b, IL-4 and TNF-a secretion) but very few signaling events have been described. To gain a better understanding of how the biologic activities of IL-16 are regulated following receptor engagement (CD4) we have analyzed the activation state of numerous STAT proteins in primary human peripheral blood mononuclear cells (PBMCs) and the human monocytic cell line THP-1 following IL-16 stimulation. Of the four STAT proteins tested, only STAT6 was activated (phosphorylated) in a dose-dependant manner by IL-16. The activation of STAT6 was completely abolished when IL-16 was pre-incubated with soluble CD4 (the IL-16 cell surface receptor), demonstrating the need for CD4 engagement in STAT6 activation. These results are the first to demonstrate a link between IL-16 and STAT6 activation. [Copyright &y& Elsevier]

Rosette-forming glioneuronal tumors (RGNTs) are rare, grade I, central nervous system (CNS) tumors typically localized to the fourth ventricle. We describe a 9-year-old girl with dizziness and occipital headache. A magnetic resonance imaging (MRI) revealed a large hypodense posterior fossa mass lesion in relation to the vermis, with cystic component. Surgical resection of the tumor was performed. A RGNT diagnosis was made at the histopathological examination. During follow-up, the patient experienced a first relapse, which was again surgically removed. Eight months after, MRI documented a second recurrence at the local level. She was a candidate for the proton beam therapy (PBT) program. Three years after the end of PBT, the patient had no evidence of disease recurrence. This report underlines that, although RGNTs are commonly associated with an indolent course, they may have the potential for aggressive behavior, suggesting the need for treatment in addition to surgery. Controversy exists in the literature regarding effective management of RGNTs. Chemotherapy and radiation are used as adjuvant therapy, but their efficacy management has not been adequately described in the literature. This is the first case report published in which PBT was proposed for adjuvant therapy in place of chemotherapy in RGNT relapse. [ABSTRACT FROM AUTHOR]

Brain tumors are the most common solid neoplasms of childhood. They are frequently reported in children with Neurofibromatosis type 1 (NF1). The most frequent central nervous system malignancies described in NF1 are optic pathway gliomas and brainstem gliomas. Medulloblastoma (MB) in NF1 patients is extremely rare, and to our knowledge, only 10 cases without molecular characterization are described in the literature to date. We report the case of a 14-year-old girl with NF1 that came to our attention for an incidental finding of a lesion arising from cerebellar vermis. The mass was completely resected, revealing a localized classic medulloblastoma (MB), subgroup 4. She was treated as a standard-risk MB with a dose-adapted personalized protocol. The treatment proved to be effective, with minor toxicity. Brain and spine MRI one year after diagnosis confirmed the complete remission of the disease. To our knowledge, this is the only case of MB reported in a patient with NF1 with molecular characterization by the methylation profile. The association between NF1 and MB, although uncommon, may not be an accidental occurrence. [ABSTRACT FROM AUTHOR]

Poster: Clinical track: CNS PO-0883: Early outcomes in patients with skull base chordomas and chondrosarcomas treated with proton therapy A. Turkaj, I. Giacomelli, M. Cianchetti, D. Scartoni, D. Amelio, S. Vennarini, B. Rombi, F. Dionisi, M. Amichetti. [Extracted from the article]