Leptomeningeal malignancy of childhood: sharing learning between childhood leukaemia and brain tumour trials.

Leptomeningeal malignancy complicates childhood cancers, including leukaemias, brain tumours, and solid tumours. In leukaemia, such malignancy is thought to invade leptomeninges via the vascular route. In brain tumours, dissemination from the primary tumour, before or after surgery, via CSF pathways is assumed; however, evidence exists to support the vascular route of dissemination. Success in treating leptomeningeal malignancy represents a rate-limiting step to cure, which has been successfully overcome in leukaemia with intensified systemic therapy combined with intra-CSF therapy, which replaced cranial radiotherapy for many patients. This de-escalated CNS-directed therapy is still associated with some neurotoxicity. The balanced benefit justifies exploration of ways to further de-escalate CNS-directed therapy. For primary brain tumours, standard therapy is craniospinal radiotherapy, but attendant risk of acute and delayed brain injury and endocrine deficiencies compounds post-radiation impairment of spinal growth. Alternative ways of treating leptomeninges by intensifying drug therapy delivered to CSF are being investigated-preliminary evidence suggests improved outcomes. This Review seeks to describe methods of intra-CSF drug delivery and drugs in use, and consider how the technique could be modified and additional drugs might be selected for this route of administration.

Universal field matching in craniospinal irradiation by a background-dose gradient-optimized method.

PURPOSE: The gradient-optimized methods are overcoming the traditional feathering methods to plan field junctions in craniospinal irradiation. In this note, a new gradient-optimized technique, based on the use of a background dose, is described. METHODS: Treatment planning was performed by RayStation (RaySearch Laboratories, Stockholm, Sweden) on the CT scans of a pediatric patient. Both proton (by pencil beam scanning) and photon (by volumetric modulated arc therapy) treatments were planned with three isocenters. An 'in silico' ideal background dose was created first to cover the upper-spinal target and to produce a perfect dose gradient along the upper and lower junction regions. Using it as background, the cranial and the lower-spinal beams were planned by inverse optimization to obtain dose coverage of their relevant targets and of the junction volumes. Finally, the upper-spinal beam was inversely planned after removal of the background dose and with the previously optimized beams switched on. RESULTS: In both proton and photon plans, the optimized cranial and the lower-spinal beams produced a perfect linear gradient in the junction regions, complementary to that produced by the optimized upper-spinal beam. The final dose distributions showed a homogeneous coverage of the targets. DISCUSSION: Our simple technique allowed to obtain high-quality gradients in the junction region. Such technique universally works for photons as well as protons and could be applicable to the TPSs that allow to manage a background dose.

Supine craniospinal irradiation using a proton pencil beam scanning technique without match line changes for field junctions.

PURPOSE: To propose and validate a craniospinal irradiation approach using a proton pencil beam scanning technique that overcomes the complexity of the planning associated with feathering match lines. METHODS AND MATERIALS: Ten craniospinal irradiation patients had treatment planned with gradient dose optimization using the proton pencil beam scanning technique. The robustness of the plans was evaluated by shifting the isocenter of each treatment field by ±3 mm in the longitudinal direction and was compared with the original nonshifted plan with metrics of conformity number, homogeneity index, and maximal cord doses. An anthropomorphic phantom study using film measurements was carried out on a plan with 5-cm junction length. To mimic setup errors in the phantom study, fields were recalculated with isocenter shifts of 1, 3, 5, and 10 mm longitudinally, and compared with the original plans and measurements. RESULTS: Uniform dose coverage to the entire target volumes was achieved using the gradient optimization approach with averaged junction lengths of 6.7 ± 0.5 cm. The average conformity number and homogeneity index equaled 0.78 ± 0.03 and 1.09 ± 0.01, respectively. Setup errors of 3 mm per field (6 mm in worst-case scenario) caused on average 4.6% lower conformity number 2.5% higher homogeneity index and maximal cord dose of 4216.1 ± 98.2 cGy. When the junction length was 5 cm or longer, setup errors of 6 mm resulted in up to 12% dosimetric deviation. Consistent results were reached between film measurements and planned dose profiles in the junction area. CONCLUSIONS: Longitudinal setup errors directly reduce the dosimetric accuracy of the proton craniospinal irradiation treatment with matched proton pencil beam scanning fields. The reported technique creates a slow dose gradient in the junction area, which makes the treatment more robust to longitudinal setup errors compared to conventional feathering methods.