Dose calculation and reporting with a linear Boltzman transport equation solver in vertebral SABR.

Vertebral Stereotactic ablative body radiotherapy (SABR) involves substantial tumour density heterogeneities. We evaluated the impact of a linear Boltzmann transport equation (LBTE) solver dose calculation on vertebral SABR dose distributions. A sequential cohort of 20 patients with vertebral metastases treated with SABR were selected. Treatment plans were initially planned with a convolution style dose calculation algorithm. The plan was copied and recalculated with a LBTE algorithm reporting both dose to water (Dw) or dose to medium (Dm). Target dose as a function of CT number, and spinal cord dose was compared between algorithms. Compared with a convolution algorithm, there was minimal change in PTV D90% with LBTE. LBTE reporting Dm resulted in reduced GTV D50% by (mean, 95% CI) 2.2% (1.9-2.6%) and reduced Spinal Cord PRV near-maximum dose by 3.0% (2.0-4.1%). LBTE reporting Dw resulted in increased GTV D50% by 2.4% (1.8-3.0%). GTV D50% decreased or increased with increasing CT number with Dm or Dw respectively. LBTE, reporting either Dm or Dw resulted in decreased central spinal cord dose by 8.7% (7.1-10.2%) and 7.2% (5.7-8.8%) respectively. Reported vertebral SABR tumour dose when calculating with an LBTE algorithm depends on tumour density. Spinal cord near-maximum dose was lower when using LBTE algorithm reporting Dm, which may result in higher spinal cord doses being delivered than with a convolution style algorithm. Spinal cord central dose was significantly lower with LBTE, potentially reflecting LBTE transport approximations.

Triggered kV Imaging During Spine SBRT for Intrafraction Motion Management.

Purpose: To monitor intrafraction motion during spine stereotactic body radiotherapy(SBRT) treatment delivery with readily available technology, we implemented triggered kV imaging using the on-board imager(OBI) of a modern medical linear accelerator with an advanced imaging package. Methods: Triggered kV imaging for intrafraction motion management was tested with an anthropomorphic phantom and simulated spine SBRT treatments to the thoracic and lumbar spine. The vertebral bodies and spinous processes were contoured as the image guided radiotherapy(IGRT) structures specific to this technique. Upon each triggered kV image acquisition, 2D projections of the IGRT structures were automatically calculated and updated at arbitrary angles for display on the kV images. Various shifts/rotations were introduced in x, y, z, pitch, and yaw. Gantry-angle-based triggering was set to acquire kV images every 45°. A group of physicists/physicians(n = 10) participated in a survey to evaluate clinical efficiency and accuracy of clinical decisions on images containing various phantom shifts. This method was implemented clinically for treatment of 42 patients(94 fractions) with 15 second time-based triggering. Result: Phantom images revealed that IGRT structure accuracy and therefore utility of projected contours during triggered imaging improved with smaller CT slice thickness. Contouring vertebra superior and inferior to the treatment site was necessary to detect clinically relevant phantom rotation. From the survey, detectability was proportional to the shift size in all shift directions and inversely related to the CT slice thickness. Clinical implementation helped evaluate robustness of patient immobilization. Based on visual inspection of projected IGRT contours on planar kV images, appreciable intrafraction motion was detected in eleven fractions(11.7%). Discussion: Feasibility of triggered imaging for spine SBRT intrafraction motion management has been demonstrated in phantom experiments and implementation for patient treatments. This technique allows efficient, non-invasive monitoring of patient position using the OBI and patient anatomy as a direct visual guide.

Use of dynamic contrast-enhanced MRI for the early assessment of outcome of CyberKnife stereotactic radiosurgery for patients with spinal metastases.

AIM: To explore the value of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for evaluating early outcomes of CyberKnife radiosurgery for spinal metastases. MATERIALS AND METHODS: Patients with spinal metastases who were treated with CyberKnife radiosurgery from July 2018 to December 2020 were enrolled. Conventional MRI and DCE-MRI were performed before treatment and at 3 months after treatment. Patients showing disease progression were defined as the progressive disease (PD) group and those showing complete response, partial response, and stable disease were defined as the non-PD group. The haemodynamic parameters (volume transfer constant [Ktrans], rate constant [Kep], and extravascular space [Ve]) before and after treatment between the groups were analysed. Area under the curve (AUC) values were calculated. RESULTS: A total of 27 patients with 39 independent spinal lesions were included. The median follow-up time was 18.6 months (6.2-36.4 months). There were 27 lesions in the non-PD group and 12 lesions in the PD group. Post-treatment Kep, ΔKtrans and ΔKep in the non-PD group (0.959/min, - 32.6% and -41.1%, respectively) were significantly lower than the corresponding values in PD group (1.429/min, 20.4% and -6%; p<0.05). Post-treatment Ve and ΔVe (0.223 and 27.8%, respectively) in the non-PD group were significantly higher than that of the PD group (0.165 and -13.5%, p<0.05). ΔKtrans showed the highest diagnostic efficiency, with an AUC of 0.821. CONCLUSIONS: DCE-MRI parameters change significantly at an early stage after CyberKnife stereotactic radiosurgery for spinal metastases. DCE-MRI may be of value in determining the early treatment response.

Monsters with a shortened vertebral column: A population phenomenon in radiating fish Labeobarbus (Cyprinidae).

The phenomenon of a massive vertebral deformity was recorded in the radiating Labeobarbus assemblage from the middle reaches of the Genale River (south-eastern Ethiopia, East Africa). Within this sympatric assemblage, five trophic morphs-generalized, lipped, piscivorous and two scraping feeders-were reported between 1993 and 2019. In 2009, a new morph with prevalence of ~10% was discovered. The new morph, termed 'short', had an abnormally shortened vertebral column and a significantly deeper body. This type of deformity is common in farmed Atlantic salmon and other artificially reared fish, but is rare in nature. In the Genale Labeobarbus assemblage, the deformity was present exclusively within the generalized and lipped morphs. The short morph had between seven and 36 deformed (compressed and/or fused) vertebrae. Their body depth was positively correlated with number of deformed vertebrae. In another collection in 2019, the short morph was still present at a frequency of 11%. Various environmental and genetic factors could contribute to the development of this deformity in the Genale Labeobarbus, but based on the available data, it is impossible to confidently identify the key factor(s). Whether the result of genetics, the environment, or both, this deep-bodied phenotype is assumed to be an anti-predator adaptation, as there is evidence of its selective advantage in the generalized morph. The Genale monstrosity is the first reported case of a massive deformity of the vertebral column in a natural population of African fishes.

Delayed Radiation Myelopathy in a Child With Hodgkin Lymphoma and ARTEMIS Mutation.

The authors present a case of delayed radiation myelopathy in a 12-year-old girl with Hodgkin lymphoma and Artemis mutation. This is the first of such a case presented in the literature.

Efficacy and toxicity of re-irradiation spine stereotactic body radiotherapy with respect to irradiation dose history.

OBJECTIVE: We aimed to clarify the outcomes of re-irradiation stereotactic body radiotherapy for spinal metastases with a uniform dose fractionation schedule at our institution. METHODS: Data of patients treated with re-irradiation stereotactic body radiotherapy for spinal metastases (September 2013-March 2020) were retrospectively reviewed. The prescribed dose was 24 Gy in two fractions. The spinal cord dose constraint and dose for previously irradiated cases ≥50 Gy in 25 fractions were 12.2 Gy (maximum dose) and 11 Gy, respectively. The endpoints were pain control, local failure and adverse effects. Pain status was measured on a scale of 0-10 using the patients' self-reports and pain response was defined using international consensus criteria. Local failure was defined as tumor progression on imaging evaluations. RESULTS: We assessed 133 lesions in 123 patients, where 70 (52.6%) had three or more spinal levels treated, 58 (43.6%) had previous irradiation doses of 40 Gy or more and 53 (39.8%) had the targets compressing the cord. The median follow-up was 12 months and the 3-, 6- and 12-month pain response rate was 75, 64 and 59%, respectively. The 1-year local failure rate was 25.8%. Previous irradiation dose was not correlated with local failure rate (P = 0.13). Radiation-induced myelopathy, radiculopathy and vertebral compression fractures were observed in 4 (3.0%), 2 (1.5%) and 17 (13.8%) lesions, respectively. A trend towards an association between any toxicity and previous irradiation dose was not observed. CONCLUSIONS: Re-irradiation spine stereotactic body radiotherapy achieved good local control and pain control, with reduced risk of radiation myelopathy.

Predictive factors of posttreatment fracture by definitive radiotherapy for uterine cervical cancer.

PURPOSE: Fractures are known to shorten life expectancy and worsen the quality of life. The risk of fractures after radiation therapy in cervical cancer patients is known to be multifactorial. In this study, we examined risk factors for fractures in cervical cancer patients, especially by evaluating bone densities and DVH parameters for fractured bones. MATERIALS AND METHODS: For 42 patients, clinical characteristics, pretreatment CT bone densities, and radiation dose were compared between patients with and without fractures. RESULTS: Posttreatment fractures occurred in 25 bones among ten patients. Pretreatment CT bone densities were significantly lower in patients with fractures (P < 0.05-0.01 across sites, except for the ilium and the ischium). Although DVH parameters were also significantly associated with fractures in univariate analysis, only CT densities were significantly associated with fractures in multivariate analysis. CONCLUSION: Pretreatment CT densities of spinal and pelvic bones, which may reflect osteoporosis, have a significant impact on the risk for posttreatment fractures.

Morphological changes in the vertebrae and central canal of rat pups born after exposure to the electromagnetic field of pregnant rats.

Several studies have investigated the effects of the electromagnetic field (EMF) on the central nervous system. However, we encountered no studies of the effects of EMF applied in the prenatal period on the offspring vertebrae. The aim of this study is to investigate the effect of a 900 megahertz (MHz) EMF applied to rat dams in the prenatal period on the vertebrae of rat pups. Female Sprague Dawley rats weighing 180-250 g were used in the experiment. Rats identified as pregnant were divided into two groups, control (n = 3) and EMF (n = 3). No EMF was applied to the control group pregnant rats. EMF was applied to the EMF group rats for 1 h daily on an equal and standard basis on prenatal days 13-21. All newborn rat pups were divided into pup control (n = 6) (PC) and pup EMF (n = 6) (PEMF) groups, and no treatment was performed on either. All animals were decapitated on day 32, and the spinal cord in the upper thoracic region was harvested. Vertebral tissues were subjected to routine histological procedures. Histopathological examination revealed that PEMF group vertebral cartilage had been converted into bone tissue. Comparison of central canal diameter and area values between the PEMF group and the PC group revealed statistically significant increases in the PEMF group (p = 0.000 and p = 0.001, respectively). Statistical analysis revealed no significant difference in mean body weights between the two groups (p > 0.530). Based on these findings, we think that 900 MHz EMF applied in the prenatal period affects the development of the vertebrae. This effect causes pathological changes in the rat pup vertebrae. These findings now raise the question of whether EMF also has an impact on neurological and neurosurgical diseases involving the vertebrae.

Spinal changes after craniospinal irradiation in pediatric patients.

BACKGROUND: To evaluate long-term degenerative changes in bone and soft tissue after craniospinal irradiation (CSI). PROCEDURE: An analysis was performed for 892 vertebral bodies in 220 pediatric patients treated with CSI. To analyze vertebral growth, vertebral body height was calculated. Signal changes for vertebral bodies on MRI, scoliosis and kyphosis, degenerative changes of vertebral bones and discs, and wedging or vertebral height loss were analyzed on images, and factors that influenced these changes were investigated. RESULTS: Vertebral growth was significantly correlated with radiation dose and growth hormone (GH) deficiency. Growth rate was significantly worse at a dose >39 Gy. Fatty marrow change was found in 83% of patients, 31% had disc degenerative changes, 13% had degenerative changes of spinal bones, 17% had wedging or spinal height loss, and 27% had scoliosis. CONCLUSIONS: Vertebral bone growth was significantly reduced when high doses were administered, and adequate GH replacement was important for bone growth. Even with symmetrical irradiation, the risk of scoliosis is high after CSI. There was also frequent progression of spinal demineralization and degenerative changes after CSI. Therefore, careful attention should be paid to spinal symptoms as pediatric patients grow into adulthood.

Outcomes after reirradiation of spinal metastasis with stereotactic body radiation therapy (SBRT): a retrospective single institutional study.

This study was aimed at assessing the feasibility and toxicity of using stereotactic body radiation therapy (SBRT) for reirradiation of spinal metastatic tumors. We conducted a retrospective review, from our institutional database, of the data of patients who received reirradiation, with overlap of some prescribed isodose lines to the vertebra from the initial radiation therapy, between 2007 and 2019. We identified 40 patients with spinal metastatic tumors, of whom 2 had 2 metastatic vertebral lesions each, totaling up to 42 target lesions. The median dose to spinal cord at the initial radiation therapy was 30 Gy. SBRT based on the intensity-modulated radiation therapy (IMRT) technique was used for reirradiation to spare the spinal cord. All patients received a prescription dose of 25 Gy in 5 fractions to the planning target volume (PTV). Among the 40 cases who had pain, pain relief was obtained in 24 (60%) after reirradiation. Neurologic improvement was obtained in 8 of 15 cases (53%). The adverse events were evaluated using the Common Terminology Criteria for Adverse Events Version 5.0. Reirradiation was well-tolerated, with only 2 patients experiencing adverse events ≥grade 2 in severity, including 1 patient with grade 3 pain, and another patient with grade 3 spinal fracture. None of the patients developed radiation myelopathy. Our data demonstrated that reirradiation of spinal metastasis using SBRT provided effective pain relief and neurologic improvement, with minimal toxicity.

Assessment of the results and hematological side effects of 3D conformal and IMRT/ARC therapies delivered during craniospinal irradiation of childhood tumors with a follow-up period of five years.

BACKGROUND: Craniospinal irradiation (CSI) of childhood tumors with the RapidArc technique is a new method of treatment. Our objective was to compare the acute hematological toxicity pattern during 3D conformal radiotherapy with the application of the novel technique. METHODS: Data from patients treated between 2007 and 2014 were collected, and seven patients were identified in both treatment groups. After establishing a general linear model, acute blood toxicity results were obtained using SPSS software. Furthermore, the exposure dose of the organs at risk was compared. Patients were followed for a minimum of 5 years, and progression-free survival and overall survival data were assessed. RESULTS: After assessment of the laboratory parameters in the two groups, it may be concluded that no significant differences were detected in terms of the mean dose exposures of the normal tissues or the acute hematological side effects during the IMRT/ARC and 3D conformal treatments. Laboratory parameters decreased significantly compared to the baseline values during the treatment weeks. Nevertheless, no significant differences were detected between the two groups. No remarkable differences were confirmed between the two groups regarding the five-year progression-free survival or overall survival, and no signs of serious organ toxicity due to irradiation were observed during the follow-up period in either of the groups. CONCLUSION: The RapidArc technique can be used safely even in the treatment of childhood tumors, as the extent of the exposure dose in normal tissues and the amount of acute hematological side effects are not higher with this technique.

Response to GH Treatment After Radiation Therapy Depends on Location of Irradiation.

OBJECTIVES: Cancer survivors with GH deficiency (GHD) receive GH therapy (GHT) after 1+ year observation to ensure stable tumor status/resolution. HYPOTHESIS: Radiation therapy (RT) to brain, spine, or extremities alters growth response to GHT. AIM: Identify differences in growth response to GHT according to type/location of RT. METHODS: The Pfizer International Growth Database was searched for cancer survivors on GHT for ≥5 years. Patient data, grouped by tumor type, were analyzed for therapy (surgery, chemotherapy, RT of the focal central nervous system, cranial, craniospinal, or total body irradiation [TBI] as part of bone marrow transplantation), sex, peak stimulated GH, age at GHT start, and duration from RT to GHT start. Kruskal-Wallis test and quantile regression modeling were performed. RESULTS: Of 1149 GHD survivors on GHT for ≥5 years (male 733; median age 8.4 years; GH peak 2.8 ng/mL), 431 had craniopharyngioma (251, cranial RT), 224 medulloblastoma (craniospinal RT), 134 leukemia (72 TBI), and 360 other tumors. Median age differed by tumor group (P < 0.001). Five-year delta height SD score (SDS) (5-year ∆HtSDS; median [10th-90th percentile]) was greatest for craniopharyngioma, 1.6 (0.3-3.0); for medulloblastoma, 5-year ∆HtSDS 0.9 (0.0-1.9); for leukemia 5-year ∆HtSDS, after TBI (0.3, 0-0.7) versus without RT (0.5, 0-0.9), direct comparison P < 0.001. Adverse events included 40 treatment-related, but none unexpected. CONCLUSIONS: TBI for leukemia had significant impact on growth response to GHT. Medulloblastoma survivors had intermediate GHT response, whereas craniopharyngioma cranial RT did not alter GHT response. Both craniospinal and epiphyseal irradiation negatively affect growth response to GH therapy compared with only cranial RT or no RT.

Deep Learning model for markerless tracking in spinal SBRT.

Stereotactic Body Radiation Therapy (SBRT), alternatively termed Stereotactic ABlative Radiotherapy (SABR) or Stereotactic RadioSurgery (SRS), delivers high dose with a sub-millimeter accuracy. It requires meticulous precautions on positioning, as sharp dose gradients near critical neighboring structures (e.g. the spinal cord for spinal tumor treatment) are an important clinical objective to avoid complications such as radiation myelopathy, compression fractures, or radiculopathy. To allow for dose escalation within the target without compromising the dose to critical structures, proper immobilization needs to be combined with (internal) motion monitoring. Metallic fiducials, as applied in prostate, liver or pancreas treatments, are not suitable in clinical practice for spine SBRT. However, the latest advances in Deep Learning (DL) allow for fast localization of the vertebrae as landmarks. Acquiring projection images during treatment delivery allows for instant 2D position verification as well as sequential (delayed) 3D position verification when incorporated in a Digital TomoSynthesis (DTS) or Cone Beam Computed Tomography (CBCT). Upgrading to an instant 3D position verification system could be envisioned with a stereoscopic kilovoltage (kV) imaging setup. This paper describes a fast DL landmark detection model for vertebra (trained in-house) and evaluates its accuracy to detect 2D motion of the vertebrae with the help of projection images acquired during treatment. The introduced motion consists of both translational and rotational variations, which are detected by the DL model with a sub-millimeter accuracy.

Outcomes of patients with spinal metastases from renal cell carcinoma treated with conventionally-fractionated external beam radiation therapy.

Renal cell carcinoma (RCC) has been traditionally thought to be radioresistant. This retrospective cohort study aims to assess the outcomes of patients with spinal metastases from RCC treated with conventionally-fractionated external beam radiation therapy (cEBRT) in our institution.Patients diagnosed with histologically or radiologically-proven RCC who received palliative cEBRT to spinal metastases, using 3-dimensional conformal technique between 2009 and 2018 were reviewed. Local progression-free survival (PFS), overall survival (OS) and common terminology criteria for adverse events version 4.0-graded toxicity were assessed. Univariable and multivariable Cox proportional hazards regression analyses were performed to evaluate for predictors associated with survivals.Thirty-five eligible patients with forty spinal segments were identified, with a median follow-up of 7 months (range, 0-47). The median equivalent dose in 2 Gy fractions (EQD2) was 32.5 Gy 10 (range, 12-39). Thirty-seven percent of patients underwent surgical intervention. At the time of last follow-up, all but 1 patient had died. Seven patients developed local progression, with the median time to local progression of 10.2 months. The median local PFS and OS were 3.3 and 4.8 months. There was no grade 3 or higher toxicity. A higher radiation dose (equivalent dose to 2 Gy fraction <32.5 Gy 10 vs ≥32.5Gy 10) (hazard ratio [HR], 0.47; 95% confidence interval [CI], 0.17-3.18; P-value (P) = .68) and spinal surgery (HR, 2.35; 95% CI, 0.53-10.29; P = .26) were not significantly associated with local PFS on univariable analysis. Multivariable analysis showed that higher Tokuhashi score (HR, 0.41; 95% CI, 0.19-0.88; P = .02), lower number of spinal segments irradiated (HR, 1.18; 95% CI, 1.01-1.37; P = .04) and use of targeted therapy (HR, 0.41; 95% CI, 0.18-0.96; P = .04) were independent predictors for improved OS.For an unselected group of patients with RCC, there is no significant association between higher radiation dose and improved local control following cEBRT. This may be due to their short survivals. With the use of more effective systemic therapy, including targeted therapy and immunotherapy, survival will likely be prolonged. A tailored-approach is needed to identify patients with good prognosis who may still benefit from aggressive local treatments.

Inter-patient variations in relative biological effectiveness for cranio-spinal irradiation with protons.

Cranio-spinal irradiation (CSI) using protons has dosimetric advantages compared to photons and is expected to reduce risk of adverse effects. The proton relative biological effectiveness (RBE) varies with linear energy transfer (LET), tissue type and dose, but a variable RBE has not replaced the constant RBE of 1.1 in clinical treatment planning. We examined inter-patient variations in RBE for ten proton CSI patients. Variable RBE models were used to obtain RBE and RBE-weighted doses. RBE was quantified in terms of dose weighted organ-mean RBE ([Formula: see text] = mean RBE-weighted dose/mean physical dose) and effective RBE of the near maximum dose (D2%), i.e. RBED2% = [Formula: see text], where subscripts RBE and phys indicate that the D2% is calculated based on an RBE model and the physical dose, respectively. Compared to the median [Formula: see text] of the patient population, differences up to 15% were observed for the individual [Formula: see text] values found for the thyroid, while more modest variations were seen for the heart (6%), lungs (2%) and brainstem (<1%). Large inter-patient variation in RBE could be correlated to large spread in LET and dose for these organs at risk (OARs). For OARs with small inter-patient variations, the results show that applying a population based RBE in treatment planning may be a step forward compared to using RBE of 1.1. OARs with large inter-patient RBE variations should ideally be selected for patient-specific biological or RBE robustness analysis if the physical doses are close to known dose thresholds.

Radiation therapy combined with bone-modifying agents ameliorates local control of osteolytic bone metastases in breast cancer.

Bone-modifying agents (BMAs) are frequently used for the treatment of bone metastases. Both BMA and radiation therapy (RT) are effective; however, there are few studies that have evaluated the efficacy of the combination treatment. We evaluated the effectiveness of RT + BMA in breast cancer-induced osteolytic bone metastasis as compared to BMA alone. A total of 43 lesions in 25 patients were evaluated. The median follow-up period was 18 (range, 2-90) months. None of the lesions was treated with chemotherapy or molecular targeted drugs during the follow-up period for evaluating the local response. Patients with complete or partial response were considered as responders, while those with stable or progressive disease were considered as non-responders. The rate of response with RT + BMA was significantly higher than that with BMA alone (P = 0.001). The cumulative incidence rate of response at 6 months was 54.4% in the RT + BMA group and 27.5% in the BMA alone group. The median time to response was 4 (range, 2-11) months in the RT + BMA group and 6 (range, 4-16) months in the BMA alone group. The overall survival rate in the responder group (83.1% at 1 year) was significantly higher than that in the non-responder group (37.5% at 1 year) (P = 0.029). In conclusion, RT combined with BMA was found to be more effective than BMA alone for the treatment of osteolytic bone metastasis, which thereby improves the prognosis.

Credentialing of vertebral stereotactic ablative body radiotherapy in a multi-centre trial.

PURPOSE/OBJECTIVE: Stereotactic ablative body radiotherapy (SABR) in multi-centre trials requires rigorous quality assurance to ensure safe and consistent treatment for all trial participants. We report results of vertebral SABR dosimetry credentialing for the ALTG/TROG NIVORAD trial. MATERIAL/METHODS: Centres with a previous SABR site visit performed axial film measurement of the benchmarking vertebral plan in a local phantom and submitted radiochromic film images for analysis. Remaining centres had on-site review of SABR processes and axial film measurement of the vertebral benchmarking plan. Films were analysed for dosimetric and positional accuracy: gamma analysis (>90% passing 2%/2mm/10% threshold) and ≤ 1 mm positional accuracy at target-cord interface was required. RESULTS: 19 centres were credentialed; 11 had on-site measurement. Delivery devices included linear accelerator, TomoTherapy and CyberKnife systems. Five centres did not achieve 90% gamma passing rate. Of these, three were out of tolerance (OOT) in low (<5Gy) dose regions and > 80% passing rate and deemed acceptable. Two were OOT over the full dose range: one elected not to remeasure; the other also had positional discrepancy greater than 1 mm and repeat measurement with a new plan was in tolerance. The original OOT was attributed to inappropriate MLC constraints. All centres delivered planned target-cord dose gradient within 1 mm. CONCLUSION: Credentialing measurements for vertebral SABR in a multi-centre trial showed although the majority of centres delivered accurate vertebral SABR, there is high value in independent audit measurements. One centre with inappropriate MLC settings was detected, which may have resulted in delivery of clinically unacceptable vertebral SABR plans.

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.

A Monte Carlo model for organ dose reconstruction of patients in pencil beam scanning (PBS) proton therapy for epidemiologic studies of late effects.

Significant efforts such as the Pediatric Proton/Photon Consortium Registry (PPCR) involving multiple proton therapy centers have been made to conduct collaborative studies evaluating outcomes following proton therapy. As a groundwork dosimetry effort for the late effect investigation, we developed a Monte Carlo (MC) model of proton pencil beam scanning (PBS) to estimate organ/tissue doses of pediatric patients at the Maryland Proton Treatment Center (MPTC), one of the proton centers involved in the PPCR. The MC beam modeling was performed using the TOPAS (TOol for PArticle Simulation) MC code and commissioned to match measurement data within 1% for range, and 0.3 mm for spot sizes. The established MC model was then tested by calculating organ/tissue doses for sample intracranial and craniospinal irradiations on whole-body pediatric computational human phantoms. The simulated dose distributions were compared with the treatment planning system dose distributions, showing the 3 mm/3% gamma index passing rates of 94%-99%, validating our simulations with the MC model. The calculated organ/tissue doses per prescribed doses for the craniospinal irradiations (1 mGy Gy-1 to 1 Gy Gy-1) were generally much higher than those for the intracranial irradiations (2.1 µGy Gy-1 to 0.1 Gy Gy-1), which is due to the larger field coverage of the craniospinal irradiations. The largest difference was observed at the adrenal dose, i.e. ∼3000 times. In addition, the calculated organ/tissue doses were compared with those calculated with a simplified MC model, showing that the beam properties (i.e. spot size, spot divergence, mean energy, and energy spread) do not significantly influence dose calculations despite the limited irradiation cases. This implies that the use of the MC model commissioned to the MPTC measurement data might be dosimetrically acceptable for patient dose reconstructions at other proton centers particularly when their measurement data are unavailable. The developed MC model will be used to reconstruct organ/tissue doses for MPTC pediatric patients collected in the PPCR.

Re-irradiation of vertebral bodies.

Improvements in clinical care and therapy mean that more patients are diagnosed and living longer with vertebral metastases. Thus, they are at risk of the development of recurrence that requires re-irradiation. Normal tissues often recover some of the damage caused by the primary radiotherapy with time and specific normal tissues can tolerate a considerable retreatment radiation dose. However, the risk of normal tissue damage and the impact on the quality of life must be considered and should be done with maximum care and accuracy especially in the vertebral area. For many years conventional external beam radiation therapy was the standard treatment modality. Fortunately, with crucial technological progress in the field of radiation oncology we are able to integrate body imaging with accurate treatment delivery methods as stereotactic body radiotherapy to improve the efficacy, shorten the overall treatment time and potentially reduce treatment-related toxicities. A short description of re-irradiation strategy covering diagnostic procedures, volume delineation, dose reconstructions, treatment planning, and guidelines are outlined. Moreover, publications on vertebral bodies re-irradiation summarizing available knowledge about toxicity, dose-volume constraints, local control, and pain response are followed. Although the knowledge is limited to a series of a single institution, it shows that re-irradiation is an effective treatment for local control and pain response. Furthermore, treatment was also shown to be safe with low risk of spinal cord damage which is one of the most worrisome toxicity.