Current practices of craniospinal irradiation techniques in Turkey: a comprehensive dosimetric analysis.

OBJECTIVE: This study evaluates various craniospinal irradiation (CSI) techniques used in Turkish centers to understand their advantages, disadvantages and overall effectiveness, with a focus on enhancing dose distribution. METHODS: Anonymized CT scans of adult and pediatric patients, alongside target volumes and organ-at-risk (OAR) structures, were shared with 25 local radiotherapy centers. They were tasked to develop optimal treatment plans delivering 36 Gy in 20 fractions with 95% PTV coverage, while minimizing OAR exposure. The same CT data was sent to a US proton therapy center for comparison. Various planning systems and treatment techniques (3D conformal RT, IMRT, VMAT, tomotherapy) were utilized. Elekta Proknow software was used to analyze parameters, assess dose distributions, mean doses, conformity index (CI), and homogeneity index (HI) for both target volumes and OARs. Comparisons were made against proton therapy. RESULTS: All techniques consistently achieved excellent PTV coverage (V95 > 98%) for both adult and pediatric patients. Tomotherapy closely approached ideal Dmean doses for all PTVs, while 3D-CRT had higher Dmean for PTV_brain. Tomotherapy excelled in CI and HI for PTVs. IMRT resulted in lower pediatric heart, kidney, parotid, and eye doses, while 3D-CRT achieved the lowest adult lung doses. Tomotherapy approached proton therapy doses for adult kidneys and thyroid, while IMRT excelled for adult heart, kidney, parotid, esophagus, and eyes. CONCLUSION: Modern radiotherapy techniques offer improved target coverage and OAR protection. However, 3D techniques are continued to be used for CSI. Notably, proton therapy stands out as the most efficient approach, closely followed by Tomotherapy in terms of achieving superior target coverage and OAR protection.

Comparative dosimetric, setup margin, and treatment time analysis between ring gantry and C-Arm linear accelerators for VMAT-based craniospinal irradiation plans.

PURPOSE: The purpose of this study is to evaluate the dosimetric and treatment delivery characteristics of volumetric modulated arc therapy technique (VMAT)-based craniospinal axis irradiation (CSI) between ring gantry Halcyon (HAL) and C-arm based Novalis Tx (NTx) linear accelerator. Set-up margin and treatment delivery time for both machines were also taken into account. MATERIALS AND METHODS: Fifteen patients, 4 females and 11 males treated between March 2019 and February 2022 within the age group 4-56 years simulated in the supine position and were planned for multiple isocentre VMAT technique in ring gantry Halcyon and C-Arm Novalis linear accelerator for 6FFF and 6 MV flatten beam energy. The number of isocenters was the same in both the machines, usually three for adult adolescent age group patients and two for pediatric patients. Total on-couch time and the patient positional shift were captured for each isocenter during each session of treatment. Margins were calculated using Herk's formula of margin = 2.5Σ +0.7σ. Dosimetry, on-couch time, and set-up margin were compared between two competing arms. RESULTS: Ninety-five percent of PTV coverage (P = 0.333), volume receiving 107% (P = 0.676), total MU (P = 0.818) in both the arms were comparable and statically insignificant. Low-dose spillage such as D20% (P = 0.212) and D50% (P = 0.008) was lesser in HAL comparable to NTx. CI and HI were statically insignificant. Out of 26 organs at risk (OAR), only 3 organs showed a statically significant dose difference. The mean and maximum setup margin in any linear direction was 0.45 and 0.53 cm for HAL and 0.37 and 0.56 cm for NTx and, variation was statistically insignificant (0.23 < P < 0.47). On-couch time was 4.0 ± 5.5 min lesser for HAL and the difference in on-couch time between the two arms was statistically different. CONCLUSION: Even though the majority of the delivery parameters such as gantry speed, dose rate, beam characteristic (flatten or unflatten), MLC width, and speed between the ring gantry HAL and C-arm NTx linear accelerators were distinctly different, they offered no or minimal difference in the dose distribution and in the setup margin. HAL gives a faster treatment time delivery, which could be crucial for some selective cases such as patients receiving treatment under general anesthesia.

Phantosmia during proton radiation and differences in frequency of phantosmia rates based on proton craniospinal irradiation technique for pediatric brain tumor patients.

BACKGROUND: Unusual olfactory perception, often referred to as "phantosmia" or "cacosmia" has been reported during brain radiotherapy (RT), but is infrequent and does not typically interfere with the ability to deliver treatment. We seek to determine the rate of phantosmia for patients treated with proton craniospinal irradiation (CSI) and identify any potential clinical or treatment-related associations. METHODS: We performed a retrospective review of 127 pediatric patients treated with CSI, followed by a boost to the brain for primary brain tumors in a single institution between 2016 and 2021. Proton CSI was delivered with passive scattering (PS) proton technique (n = 53) or pencil beam scanning technique (PBS) (n = 74). Within the PBS group, treatment delivery to the CSI utilized a single posterior (PA) field (n = 24) or two posterior oblique fields (n = 50). We collected data on phantom smell, nausea/vomiting, and the use of medical intervention. RESULTS: Our cohort included 80 males and 47 females. The median age of patients was 10 years (range: 3-21). Seventy-one patients (56%) received concurrent chemotherapy. During RT, 104 patients (82%) developed worsening nausea, while 63 patients (50%) reported episodes of emesis. Of those patients who were awake during CSI (n = 59), 17 (29%) reported phantosmia. In the non-sedated group, we found a higher rate of phantosmia in patients treated with PBS (n = 16, 42%) than PS (n = 1, 4.7%) (p = .002). Seventy-eight patients (61%) required medical intervention after developing nausea/vomiting or phantosmia during RT. Two patients required sedation due to the malodorous smell during CSI. We did not find any significant difference in nausea/vomiting based on treatment technique. CONCLUSION: Proton technique significantly influenced olfactory perception with greater rates of phantosmia with PBS compared to PS. Prospective studies should be performed to determine the cause of these findings and determine techniques to minimize phantosmia during radiation therapy.

Performance analysis and knowledge-based quality assurance of critical organ auto-segmentation for pediatric craniospinal irradiation.

Craniospinal irradiation (CSI) is a vital therapeutic approach utilized for young patients suffering from central nervous system disorders such as medulloblastoma. The task of accurately outlining the treatment area is particularly time-consuming due to the presence of several sensitive organs at risk (OAR) that can be affected by radiation. This study aimed to assess two different methods for automating the segmentation process: an atlas technique and a deep learning neural network approach. Additionally, a novel method was devised to prospectively evaluate the accuracy of automated segmentation as a knowledge-based quality assurance (QA) tool. Involving a patient cohort of 100, ranging in ages from 2 to 25 years with a median age of 8, this study employed quantitative metrics centered around overlap and distance calculations to determine the most effective approach for practical clinical application. The contours generated by two distinct methods of atlas and neural network were compared to ground truth contours approved by a radiation oncologist, utilizing 13 distinct metrics. Furthermore, an innovative QA tool was conceptualized, designed for forthcoming cases based on the baseline dataset of 100 patient cases. The calculated metrics indicated that, in the majority of cases (60.58%), the neural network method demonstrated a notably higher alignment with the ground truth. Instances where no difference was observed accounted for 31.25%, while utilization of the atlas method represented 8.17%. The QA tool results showed that the two approaches achieved 100% agreement in 39.4% of instances for the atlas method and in 50.6% of instances for the neural network auto-segmentation. The results indicate that the neural network approach showcases superior performance, and its significantly closer physical alignment to ground truth contours in the majority of cases. The metrics derived from overlap and distance measurements have enabled clinicians to discern the optimal choice for practical clinical application.

Craniospinal irradiation for CNS leukemia: rates of response and durability of CNS control.

PURPOSE: Management of CNS involvement in leukemia may include craniospinal irradiation (CSI), though data on CSI efficacy are limited. METHODS: We retrospectively reviewed leukemia patients who underwent CSI at our institution between 2009 and 2021 for CNS involvement. CNS local recurrence (CNS-LR), any recurrence, progression-free survival (PFS), CNS PFS, and overall survival (OS) were estimated. RESULTS: Of thirty-nine eligible patients treated with CSI, most were male (59%) and treated as young adults (median 31 years). The median dose was 18 Gy to the brain and 12 Gy to the spine. Twenty-five (64%) patients received CSI immediately prior to allogeneic hematopoietic cell transplant, of which 21 (84%) underwent total body irradiation conditioning (median 12 Gy). Among 15 patients with CSF-positive disease immediately prior to CSI, all 14 assessed patients had pathologic clearance of blasts (CNS-response rate 100%) at a median of 23 days from CSI start. With a median follow-up of 48 months among survivors, 2-year PFS and OS were 32% (95% CI 18-48%) and 43% (95% CI 27-58%), respectively. Only 5 CNS relapses were noted (2-year CNS-LR 14% (95% CI 5-28%)), which occurred either concurrently or after a systemic relapse. Only systemic relapse after CSI was associated with higher risk of CNS-LR on univariate analysis. No grade 3 or higher acute toxicity was seen during CSI. CONCLUSION: CSI is a well-tolerated and effective treatment option for patients with CNS leukemia. Control of systemic disease after CSI may be important for CNS local control. CNS recurrence may reflect reseeding from the systemic space.

Automating the Treatment Planning Process for Volumetric Modulated Arc Therapy Craniospinal Irradiation.

PURPOSE: The purpose of this work is to develop a method to automate the treatment planning process of craniospinal irradiation (CSI) using volumetric modulated arc therapy. METHODS AND MATERIALS: Two scripts were developed using the Eclipse Scripting Application Programming Interface to perform auto-plan preparation and optimization. Ten patients (age, 5-44 years) previously treated at our institution with low dose volumetric modulated arc therapy CSI (prescription of 12 Gy) before total body irradiation were selected to evaluate the efficacy of the proposed auto-planning process. Paired t tests compared the dosimetric indices of the auto-plans to the manually generated clinical plans. All plans were normalized to 95% of planning target volume (PTV) coverage with the prescription dose. Two physicians and one physicist were asked to evaluate the manual plans and auto-plans of each patient in a blinded retrospective review and to indicate clinical acceptability and which plans were preferred for treatment. RESULTS: Compared with the manual CSI plans, the auto plans obtained significant reductions in Dmean to the parotids, submandibular glands, larynx, thyroid, and significant reduction in the plan PTV Dmax and D0.03 cc. The standard deviation range of the dosimetric parameters was greatly reduced for auto plans (range, 0.1-1.3 Gy) relative to manual plans (range, 0.4-5.9 Gy) indicating better plan consistency. Among the 10 patients, the auto-plans were preferred over the manual plans 90% of the time by the reviewing experts. The required time for auto-planning was approximately 1 hour compared with estimated 4 or more hours for manual planning. CONCLUSIONS: Reductions in planning time without sacrifices in plan quality were obtained using the auto-planning process compared with manual planning. Variation in plan quality was also reduced. The auto-planning scripts will be made freely available to other institutions and clinics.

Comparison of passive-scattered and intensity-modulated proton beam therapy of craniospinal irradiation with proton beams for pediatric and young adult patients with brain tumors.

PURPOSE: To investigate the dose stability of craniospinal irradiation based on irradiation method of proton beam therapy (PBT). METHODS AND MATERIALS: Twenty-four pediatric and young adult brain tumor patients (age: 1-24 years) were examined. Treatment method was passive-scattered PBT (PSPT) in 8 patients and intensity-modulated PBT (IMPT) in 16 patients. The whole vertebral body (WVB) technique was used in 13 patients whose ages were younger than 10, and vertebral body sparing (VBS) technique was used for the remaining 11 patients aged 10 and above. Dose stability of planning target volume (PTV) against set-up error was investigated. RESULTS: The minimum dose (Dmin) of IMPT was higher than that of PSPT (p = 0.01). Inhomogeneity index (INH) of IMPT was lower than that of PSPT (p = 0.004). When the irradiation field of the cervical spinal cord level (C level) was shifted, the maximum dose (Dmax) was lower in IMPT, and mean dose (Dmean) was higher than PSPT as movement became greater to the cranial-caudal direction (p = 0.000-0.043). Dmin was higher and INH was lower in IMPT in all directions (p = 0.000-0.034). When the irradiation field of the lumber spinal cord level (L level) was shifted, Dmax was lower in IMPT as movement became greater to the cranial direction (p = 0.000-0.028). Dmin was higher and INH was lower in IMPT in all directions (p = 0.000-0.022). CONCLUSIONS: The PTV doses of IMPT and PSPT are robust and stable in both anterior-posterior and lateral directions at both C level and L level, but IMPT is more robust and stable than PSPT for cranial-caudal movements. TRIAL REGISTRY: Clinical Trial Registration number: No. 04-03.

Proton pencil beam scanning craniospinal irradiation (CSI) with a single posterior brain beam: Dosimetry and efficiency.

This study explores the feasibility and potential dosimetric and time efficiency benefit of proton Pencil Beam Scanning (PBS) craniospinal irradiation with a single posterior-anterior (SPA) brain field. The SPA approach was compared to our current clinical protocol using Bilateral Posterior Oblique brain fields (BPO). Ten consecutive patients were simulated in the head-first supine position on a long BOS frame and scanned using 3 mm CT slice thickness. A customized thermoplastic mask immobilized the patient's head, neck, and shoulders. A vac-lock was used to secure the legs. PBS proton plans were robustly optimized with 3mm setup errors and 3.5% range uncertainties in the Eclipse V15.6 treatment planning system (n = 12 scenarios). In order to achieve a smooth gradient dose match at the junction area, at least 5 cm overlap region was maintained between the segments and 5 mm uncertainty along the cranial-cauda direction was applied to each segment independently as additional robust optimization scenarios. The brain doses were planned by SPA or BPO fields. All spine segments were planned with a single PA field. Dosimetric differences between the BPO and SPA approaches were compared, and the treatment efficiency was analyzed according to timestamps of beam delivery. Results: The maximum brain dose increases to 111.1 ± 2.1% for SPA vs. 109.0 ± 1.7% for BPO (p < 0.01). The dose homogeneity index (D5/D95) in brain CTV was comparable between techniques (1.037 ± 0.010 for SPA and 1.033 ± 0.008 for BPO). Lens received lower maximum doses by 2.88 ± 1.58 Gy (RBE) (left) and 2.23 ± 1.37 Gy (RBE) (right) in the SPA plans (p < 0.01). No significant cochlea dose change was observed. SPA reduced the treatment time by more than 4 minutes on average and ranged from 2 to 10 minutes, depending on the beam waiting and allocation time. SPA is dosimetrically comparable to BPO, with reduced lens doses at the cost of slightly higher dose inhomogeneity and hot spots. Implementation of SPA is feasible and can help to improve the treatment efficiency of PBS CSI treatment.

Verschlimmbesserung: Craniospinal Radiotherapy Is Essential in WNT Medulloblastoma Patients.

Standard-risk WNT medulloblastoma patients have an excellent prognosis (>90% progression-free survival) using the combination of standard dose craniospinal radiotherapy (CSI) (23.4 Gy) followed by platinum and alkylator based chemotherapy. A recent pilot study that attempted to completely omit radiotherapy was terminated early as all patients (n = 3) relapsed rapidly (on treatment or within 6 months of completing treatment). The study highlights that therapy is the most important prognostic factor, with CSI still required to cure even the most favorable subgroup of medulloblastoma patients. See related article by Cohen et al., p. 5031.

Subtyping of Group 3/4 medulloblastoma as a potential prognostic biomarker among patients treated with reduced dose of craniospinal irradiation: a Japanese Pediatric Molecular Neuro-Oncology Group study.

BACKGROUND: One of the most significant challenges in patients with medulloblastoma is reducing the dose of craniospinal irradiation (CSI) to minimize neurological sequelae in survivors. Molecular characterization of patients receiving lower than standard dose of CSI therapy is important to facilitate further reduction of treatment burden. METHODS: We conducted DNA methylation analysis using an Illumina Methylation EPIC array to investigate molecular prognostic markers in 38 patients with medulloblastoma who were registered in the Japan Pediatric Molecular Neuro-Oncology Group and treated with reduced-dose CSI. RESULTS: Among the patients, 23 were classified as having a standard-risk and 15 as high-risk according to the classic classification based on tumor resection rate and presence of metastasis, respectively. The median follow-up period was 71.5 months (12.0-231.0). The median CSI dose was 18 Gy (15.0-24.0) in both groups, and 5 patients in the high-risk group received a CSI dose of 18.0 Gy. Molecular subgrouping revealed that the standard-risk cohort included 5 WNT, 2 SHH, and 16 Group 3/4 cases; all 15 patients in the high-risk cohort had Group 3/4 medulloblastoma. Among the patients with Group 3/4 medulloblastoma, 9 of the 31 Group 3/4 cases were subclassified as subclass II, III, and V, which were known to an association with poor prognosis according to the novel subtyping among the subgroups. Patients with poor prognostic subtype showed worse prognosis than that of others (5-year progression survival rate 90.4% vs. 22.2%; p < 0.0001). The result was replicated in the multivariate analysis (hazard ratio12.77, 95% confidence interval for hazard ratio 2.38-99.21, p value 0.0026 for progression-free survival, hazard ratio 5.02, 95% confidence interval for hazard ratio 1.03-29.11, p value 0.044 for overall survival). CONCLUSION: Although these findings require validation in a larger cohort, the present findings suggest that novel subtyping of Group 3/4 medulloblastoma may be a promising prognostic biomarker even among patients treated with lower-dose CSI than standard treatment.

Proton craniospinal irradiation with bevacizumab and pembrolizumab for leptomeningeal disease: a case report.

Leptomeningeal disease (LMD) remains a challenging condition with a dismal prognosis. In this case study, we report partial response of LMD in a patient with metastatic large cell neuroendocrine carcinoma following treatment with proton craniospinal irradiation (CSI), bevacizumab, and pembrolizumab. Two years after the initial diagnosis, he presented with LMD. He underwent proton CSI with bevacizumab followed by combination therapy with pembrolizumab and bevacizumab. He had a partial disease response with progression-free survival after LMD diagnosis of 4.6 months. He unfortunately developed pembrolizumab induced hypophysitis, after which he experienced rapid neurologic clinical progression. Overall, this novel combination led to a durable partial response which warrants prospective evaluation.

Patients with leptomeningeal disease have few therapeutic options and poor treatment outcomes. Single-agent therapies have not yet been as successful in improving patient survival. In this paper, we discuss how combination therapy with proton craniospinal irradiation, bevacizumab, and pembrolizumab led to neurological improvement and disease regression. These results show that this novel combination may lead to a significant benefit not seen previously with these individual drugs given alone. We hope to lay a foundation for a novel therapeutic approach in a critically high need disease which has previously been thought to be resistant to radiotherapy or immunotherapy.

Molecular characterization of long-term survivors of metastatic medulloblastoma treated with reduced-dose craniospinal irradiation.

BACKGROUND AND AIMS: Current standard treatment for metastatic medulloblastoma consists of 36 Gray (Gy) of craniospinal irradiation (CSI) supplemented with local irradiation and adjuvant chemotherapy after surgery. Although contemporary protocols have been designed to limit a radiation dose using risk-adapted CSI dosing to reduce neurocognitive morbidity, high-dose CSI remains the standard of care. Recently, the molecular classification of medulloblastoma has been emerging but its clinical significance has not been established particularly in patients with metastatic medulloblastoma treated with lower dose of CSI. METHODS: We molecularly analyzed three cases of metastatic medulloblastoma treated with 24.0 Gy of CSI by DNA methylation analysis using the Illumina EPIC array. RESULTS: All three patients had spinal metastases at the time of diagnosis. Postoperative treatment included multiple courses of chemotherapy, 24 Gy of CSI with focal boost to primary and metastatic sites, and high-dose chemotherapy. There was no disease progression observed during the 9.0, 7.7, and 5.7　years post-diagnosis follow-up. The molecular diagnosis was Group 3/4 in all three cases. Cases 1 and 2 belonged to Subtypes 7 and 4, both of which were reported to be good prognostic subtypes among the group. Case 3 belonged to Subtype 5 with MYC amplification. CONCLUSIONS: The present cases suggest that the novel subtype classification in Group 3/4 medulloblastoma may be useful for risk stratification of patients with metastatic medulloblastoma who received lower dose of CSI than standard treatment.

Focal versus craniospinal radiation for disseminated atypical teratoid/rhabdoid tumor following favorable response to systemic therapy.

PURPOSE: Radiotherapy (RT) is associated with improved survival in atypical teratoid/rhabdoid tumor (ATRT); however, optimal RT delivery is unknown. A meta-analysis was conducted for disseminated (M+) ATRT receiving focal or craniospinal radiation (CSI). METHODS: After abstract screening, 25 studies (1995-2020) contained necessary patient, disease, and radiation treatment information (N = 96). All abstract, full text, and data capture were independently double-reviewed. The corresponding author was contacted for cases of insufficient information. Response to pre-radiation chemotherapy (N = 57) was categorized as complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD). Univariate and multivariate statistics were performed to investigate survival correlation. Patients with M4 disease were excluded. RESULTS: The 2- and 4-year overall survival (OS) was 63.8% and 45.7%, respectively, with a median follow-up of 2 years (range 0.3-13.5). The median age was 2 years (range 0.2-19.5), and 96% received chemotherapy. On univariate analysis, gross total resection (GTR, p = .0007), pre-radiation chemotherapy response (p < .001), and high-dose chemotherapy with stem cell recuse (HDSCT, p = .002) correlated with survival. On multivariate analysis, pre-radiation chemotherapy response (p = .02) and GTR (p = .012) retained survival significance as compared to a trend for HDSCT (p = .072). Comparisons of focal RT (vs. CSI) and greater than or equal to 5400 cGy primary dose were nonsignificant. Following CR or PR, a statistical trend favored focal radiation (p = .089) over CSI. CONCLUSION: Chemotherapy response prior to RT and GTR correlated with improved survival on multivariate analysis for ATRT M+ receiving RT. No benefit was observed for CSI compared to focal RT among all patients and following favorable chemotherapy response, inviting further study of focal RT for ATRT M+.

Genetic susceptibility to cognitive decline following craniospinal irradiation for pediatric central nervous system tumors.

BACKGROUND: Survivors of pediatric central nervous system (CNS) tumors treated with craniospinal irradiation (CSI) exhibit long-term cognitive difficulties. Goals of this study were to evaluate longitudinal effects of candidate and novel genetic variants on cognitive decline following CSI. METHODS: Intelligence quotient (IQ), working memory (WM), and processing speed (PS) were longitudinally collected from patients treated with CSI (n = 241). Genotype-by-time interactions were evaluated using mixed-effects linear regression to identify common variants (minor allele frequency > 1%) associated with cognitive performance change. Novel variants associated with cognitive decline (P < 5 × 10-5) in individuals of European ancestry (n = 163) were considered replicated if they demonstrated consistent genotype-by-time interactions (P < .05) in individuals of non-European ancestries (n = 78) and achieved genome-wide statistical significance (P < 5 × 10-8) in a meta-analysis across ancestry groups. RESULTS: Participants were mostly males (65%) diagnosed with embryonal tumors (98%) at a median age of 8.3 years. Overall, 1150 neurocognitive evaluations were obtained (median = 5, range: 2-10 per participant). One of the five loci previously associated with cognitive outcomes in pediatric CNS tumors survivors demonstrated significant time-dependent IQ declines (PPARA rs6008197, P = .004). Two variants associated with IQ in the general population were associated with declines in IQ after Bonferroni correction (rs9348721, P = 1.7 × 10-5; rs31771, P = 7.8 × 10-4). In genome-wide analyses, we identified novel loci associated with accelerated declines in IQ (rs116595313, meta-P = 9.4 × 10-9), WM (rs17774009, meta-P = 4.2 × 10-9), and PS (rs77467524, meta-P = 1.5 × 10-8; rs17630683, meta-P = 2.0 × 10-8; rs73249323, meta-P = 3.1 × 10-8). CONCLUSIONS: Inherited genetic variants involved in baseline cognitive functioning and novel susceptibility loci jointly influence the degree of treatment-associated cognitive decline in pediatric CNS tumor survivors.

Comparative dosimetric analysis of volumetric modulated arc therapy based craniospinal irradiation plans between Halcyon ring gantry and TrueBeam C-arm linear accelerator.

This study evaluates the volumetric modulated arc therapy (VMAT) dosimetric comparison between Halcyon ring gantry and TrueBeam c-arm linear accelerators for craniospinal irradiation (CSI) of the neuro-axis. 25 patients, who received treatment for medulloblastoma and primitive neuro-ectodermal tumors between 2018 and 2021, were planned for VMAT in True Beam (TB), and Halcyon (HAL) linear accelerators using 6 MV unflattened (FFF) photon beams (HALFFF and TBFFF). Dose-volume statistics for the target and organs at risk (OARs) and the total number of monitoring units (MUs) in the treatment plans were compared which included dose received by 95% PTV volume (V95%), volume receiving ≥ 107% dose, homogeneity index (HI), conformity index (PI), MU and dose spillage (D10%, D30%, D50%, D70%, D90%). In all 26 OARs were considered of which five were serial and the remaining were parallel structures. For the former, the dose received by 0.2 cm3, volume = D0.2 cm3) were evaluated and for the latter mean dose were evaluated. Both arms were statistically compared with paired sample t-test with a significant value of ≤ 0.05. 11 patients received treatment with the Halcyon and the rest 14 in the TrueBeam C-arm linear accelerator. Patients in the low- and intermediate-risk category (n = 13) received 23.4 Gy in 13 fractions. The remaining patients were in the high-risk category and received 35 Gy in 21 fractions or 36 Gy in 20 fractions. For HALFFF and TBFFF, PTVV95% were 97.5 ± 0.8% and 97.4 ± 0.9% respectively (p = 0.371) while the V107% were 0.6 ± 0.4% and 0.5 ± 0.5 respectively (p = 0.504). However, the number of monitoring units showed statistical significance (p < 0.001) with values of 1331.9 ± 243.4 MU and 1089 ± 206.7 MU respectively for the HAL and TB plans. The differences in spillage dose were also statistically significant, favouring HAL plans at D30% (p = 0.002), D50% (p < 0.001), D70% (p = 0.039), and D90% (p = 0.01) level except for D10% (p = 0.090). Conformity index also showed statistical significance with PI_HAL = 0.9 ± 0.02 and PI_TB = 0.89 ± 0.03 (p = 0.029). For 10 of the 21 parallel structures, the mean dose differences were statistically significant in favouring of HAL plans. Halcyon based VMAT CSI plans are dosimetrically superior in terms of organ dose, especially for the large organs, and offer lower spillage doses than the TrueBeam plans. Plans generated by both linear accelerators are suitable for the patients' treatments.

Salvage craniospinal irradiation for recurrent intracranial germinoma: a single institution analysis.

This study investigated the effectiveness and safety of low-dose salvage craniospinal irradiation (CSI) for recurrent germinoma. We retrospectively reviewed long-term tumor control and late adverse effects in 15 recurrent germinoma patients treated at our hospital between 1983 and 2019. Following the first recurrence of germinoma, seven were treated with 24-30 Gy of salvage CSI, three underwent non-CSI, and five were treated with only chemotherapy. CSI achieved a significantly better recurrence-free survival rate after the first recurrence compared to other strategies (100% vs 33%, p < 0.001: log-rank test). To evaluate the safety of salvage CSI, we assessed the outcomes at the final follow-up of seven patients who received salvage CSI at first recurrence and three patients who received salvage CSI at second recurrence. The median follow-up period was 220 months after initial treatment. Five patients who received 40-50 Gy of radiation therapy or underwent multiple radiation therapy before salvage CSI were classified into Group A, whereas five patients treated with platinum-based chemotherapy and 24-32 Gy of radiation therapy to the primary site, whole ventricle, or whole brain were classified into Group B. In Group A, one had endocrine dysfunction and the other had visual dysfunction. None were socially independent. Meanwhile, in Group B, no endocrine or visual dysfunction was found, and three patients were socially independent. Salvage CSI achieved excellent tumor control in recurrent germinoma and was safe in patients initially treated with low-dose radiation therapy and chemotherapy.

Automating the treatment planning process for 3D-conformal pediatric craniospinal irradiation therapy.

PURPOSE: Pediatric patients with medulloblastoma in low- and middle-income countries (LMICs) are most treated with 3D-conformal photon craniospinal irradiation (CSI), a time-consuming, complex treatment to plan, especially in resource-constrained settings. Therefore, we developed and tested a 3D-conformal CSI autoplanning tool for varying patient lengths. METHODS AND MATERIALS: Autocontours were generated with a deep learning model trained:tested (80:20 ratio) on 143 pediatric medulloblastoma CT scans (patient ages: 2-19 years, median = 7 years). Using the verified autocontours, the autoplanning tool generated two lateral brain fields matched to a single spine field, an extended single spine field, or two matched spine fields. Additional spine subfields were added to optimize the corresponding dose distribution. Feathering was implemented (yielding nine to 12 fields) to give a composite plan. Each planning approach was tested on six patients (ages 3-10 years). A pediatric radiation oncologist assessed clinical acceptability of each autoplan. RESULTS: The autocontoured structures' average Dice similarity coefficient ranged from .65 to .98. The average V95 for the brain/spinal canal for single, extended, and multi-field spine configurations was 99.9% ± 0.06%/99.9% ± 0.10%, 99.9% ± 0.07%/99.4% ± 0.30%, and 99.9% ± 0.06%/99.4% ± 0.40%, respectively. The average maximum dose across all field configurations to the brainstem, eyes (L/R), lenses (L/R), and spinal cord were 23.7 ± 0.08, 24.1 ± 0.28, 13.3 ± 5.27, and 25.5 ± 0.34 Gy, respectively (prescription = 23.4 Gy/13 fractions). Of the 18 plans tested, all were scored as clinically acceptable as-is or clinically acceptable with minor, time-efficient edits preferred or required. No plans were scored as clinically unacceptable. CONCLUSION: The autoplanning tool successfully generated pediatric CSI plans for varying patient lengths in 3.50 ± 0.4 minutes on average, indicating potential for an efficient planning aid in a resource-constrained settings.

A Script-Based Automatic Intensity Modulated Radiation Therapy Planning Method With Robust Optimization for Craniospinal Irradiation.

This report describes a script-based automatic planning method with robust optimization for craniospinal irradiation (CSI) to reduce sensitivity to field matching errors and increase planning efficiency. The data of 10 CSI patients with planning target volume (PTV) lengths between 49.8 and 85.0 cm were retrospectively studied. Robust intensity modulated radiation therapy plans with ±5-mm longitudinal position uncertainty were generated by the automatic planning script. A simple dose prediction model and a self-adjusting method were implied in the automatic plans. The plans' robustness against setup errors was evaluated by deliberately shifting the middle beamset ±5 mm in the superior-inferior direction. Manual and nonrobust plans were also created to evaluate the automatic robust plans' quality, efficiency, and robustness. There were no significant differences between the manual and automatic plans in terms of homogeneity index; conformity index; D1%, D2%, and D98% of PTV; and average doses of organs at risk. However, the D99% of the PTV in the automatic plans was slightly inferior to that in the manual plans. Compared with the manual plans, the automatic plans greatly increased efficiency, with a reduction in planning time of approximately 48%. When ±5-mm superior-inferior errors were introduced, the average deviations of the maximum dose D1% and minimum dose D99% to the spinal cord were 4.9% (±1.1%) and -3.4% (±1.3%), respectively. However, the corresponding values of the nonrobust plans were 20.0% (±5.4%) and -21.2 (±6.3%), respectively. The script-based automatic CSI planning method, combining robust optimization and a dose prediction model, efficiently created a good-quality plan that was robust to setup errors.

Late Effects of Craniospinal Irradiation Using Electron Spinal Fields for Pediatric Patients With Cancer.

PURPOSE: For children, craniospinal irradiation (CSI) with photons is associated with significant toxic effects. The use of electrons for spinal fields is hypothesized to spare anterior structures but the long-term effects remain uncertain. We studied late effects of CSI using electrons for spinal radiation therapy (RT). METHODS AND MATERIALS: Records of 84 consecutive patients treated with CSI using electrons for the spine at a single institution between 1983 and 2014 were reviewed. Median age at RT was 5 (range, 1-14) years. The most common histologies were medulloblastoma/primitive neuroectodermal tumor (59%) and ependymoma (8%). The median prescribed dose to the entire spine was 30 Gy (range, 6-45). A subset of 48 (57%) patients aged 2 to 14 at RT with clinical follow-up for ≥5 years was analyzed for late effects. Height z scores adjusted for age before and after CSI were assessed using stature-for-age charts and compared with a t test. RESULTS: At median follow-up of 19 years (range, 0-38 years), the median survival was 22 years (95% confidence interval, 12-28 years) after RT, with 47 patients (56%) alive at last follow-up. On subset analysis for late effects, 19 (40%) patients developed hypothyroidism and 5 (10%) developed secondary malignancies. Other complications reported were esophageal stricture and periaortic hemorrhage in 1 and restrictive pulmonary disease in 1 patient. Median height z score before treatment was -0.4 (36th percentile; interquartile range, -1.0 to 0.0) and at last follow-up was -2.2 (first percentile; interquartile range, -3.1 to -1.6; P < .001). Of 44 patients with spinal curvature assessments, 15 (34%) had scoliosis with median Cobb angle 15° (range, 10°-35°) and 1 (2%) required surgery. CONCLUSIONS: Frequent musculoskeletal toxic effects and predominantly decreased height were seen with long-term follow-up. Scoliosis and hypothyroidism were each seen in at least one-third of long-term survivors. However, clinically evident esophageal, pulmonary, and cardiac toxic effects were infrequent.