Search Results (17)

Background/Objectives. Adult medulloblastoma (AMB) patients should receive postoperative craniospinal irradiation (CSI) as a standard treatment. Volumetric intensity-modulated arc therapy (VMAT) is a promising method for CSI. This report summarizes the repositioning and dosimetric data outcomes for six AMB patients. Methods. Complete CSI and posterior cranial fossa irradiation, or tumor bed boost irradiation with Linac-based VMAT, was performed and evaluated. Patients were immobilized in the supine position with two thermoplastic masks (head-neck and abdomen). To ensure inter-fraction reproducibility during radiotherapy (RT), a single cone-beam CT (CBCT) scan for each isocenter and real-time surface-guided RT using AlignRT^® were performed daily before and during the RT session. Match values of all three translational axes (x = lateral, y = longitudinal, z = vertical) were recorded. Results. From August 2022 to September 2023, six AMB patients were treated with CSI: three women and three men with a median age of 32 (22–42). All cases were classical MB, four were low risk, and two were defined as high risk due to the metastatic disease. All patients underwent surgery; two received a gross total resection. Low-risk patients received 36 Gy for CSI and a 54 Gy boost, while high-risk patients received 39 Gy for CSI. No significant toxicities greater than G2 were observed during RT, and only two cases reported decreased platelet counts. The dose to the organs at risk was low and acceptable. The mean dose to the heart, lungs, eyes, stomach, and thyroid were 4.4 Gy, 8.5 Gy, 12 Gy, 8.7 Gy, and 11 Gy, respectively. In terms of repositioning data, 124 CBCT scans were analyzed. Inter-fraction CBCT mean values for the study population in all translational directions were inferior to 2 mm in more than 90% of cases. Conclusions. VMAT is a convenient and effective treatment for AMB. Positioning and immobilization with masks (head and neck plus abdomen) reduce inter-fraction motion. Full article

Leptomeningeal disease (LMD) is a devastating sequelae of metastatic spread that affects approximately 5% of cancer patients. The incidence of LMD is increasing due to advancements in systemic therapy and enhanced detection methods. The purpose of this review is to provide a detailed overview of the evidence in the detection, prognostication, and treatment of LMD. A comprehensive literature search of PUBMED was conducted to identify articles reporting on LMD including existing data and ongoing clinical trials. We found a wide array of treatment options available for LMD including chemotherapy, targeted agents, and immunotherapy as well as several choices for radiotherapy including whole brain radiotherapy (WBRT), stereotactic radiosurgery (SRS), and craniospinal irradiation (CSI). Despite treatment, the prognosis for patients with LMD is dismal, typically 2–4 months on average. Novel therapies and combination approaches are actively under investigation with the aim of improving outcomes and quality of life for patients with LMD. Recent prospective data on the use of proton CSI for patients with LMD have demonstrated its potential survival benefit with follow-up investigations underway. There is a need for validated metrics to predict prognosis and improve patient selection for patients with LMD in order to optimize treatment approaches. Full article

Background: Radiotherapy (RT) involving craniospinal irradiation (CSI) is important in the initial treatment of medulloblastoma. At recurrence, the re-irradiation options are limited and associated with severe side-effects. Methods: For pre-irradiated patients, patients with re-irradiation (RT2) were matched by sex, histology, time to recurrence, disease status and treatment at recurrence to patients without RT2. Results: A total of 42 pre-irradiated patients with RT2 were matched to 42 pre-irradiated controls without RT2. RT2 improved the median PFS [21.0 (CI: 15.7–28.7) vs. 12.0 (CI: 8.1–21.0) months] and OS [31.5 (CI: 27.6–64.8) vs. 20.0 (CI: 14.0–36.7) months]. Concerning long-term survival after ten years, RT2 only lead to small improvements in OS [8% (CI: 1.4–45.3) vs. 0%]. RT2 improved survival most without (re)-resection [PFS: 17.5 (CI: 9.7–41.5) vs. 8.0 (CI: 6.6–12.2)/OS: 31.5 (CI: 27.6–NA) vs. 13.3 (CI: 8.1–20.1) months]. In the RT-naïve patients, CSI at recurrence improved their median PFS [25.0 (CI: 16.8–60.6) vs. 6.6 (CI: 1.5–NA) months] and OS [40.2 (CI: 18.7–NA) vs. 12.4 (CI: 4.4–NA) months]. Conclusions: RT2 could improve the median survival in a matched cohort but offered little benefit regarding long-term survival. In RT-naïve patients, CSI greatly improved their median and long-term survival. Full article

Proton therapy is a promising modality for craniospinal irradiation (CSI), offering dosimetric advantages over conventional treatments. While significant attention has been paid to spine fields, for the brain fields, only dose reduction to the lens of the eye has been reported. Hence, the objective of this study is to assess the potential gains and feasibility of adopting different treatment planning techniques for the entire brain within the CSI target. To this end, eight previously treated CSI patients underwent retrospective replanning using various techniques: (1) intensity modulated proton therapy (IMPT) optimization, (2) the modification/addition of field directions, and (3) the pre-optimization removal of superficially placed spots. The target coverage robustness was evaluated and dose comparisons for lenses, cochleae, and scalp were conducted, considering potential biological dose increases. The target coverage robustness was maintained across all plans, with minor reductions when superficial spot removal was utilized. Single- and multifield optimization showed comparable target coverage robustness and organ-at-risk sparing. A significant scalp sparing was achieved in adults but only limited in pediatric cases. Superficial spot removal contributed to scalp V30 Gy reduction at the expense of lower coverage robustness in specific cases. Lens sparing benefits from multiple field directions, while cochlear sparing remains impractical. Based on the results, all investigated plan types are deemed clinically adoptable. Full article

Craniospinal irradiation (CSI) has been a major component of the standard of care treatment backbone for childhood medulloblastoma. However, chemotherapy regimens have varied based on protocol, patient age, and molecular subtyping. In one of the largest studies to date, we analyzed treatment outcomes in children with newly-diagnosed medulloblastoma treated with pre-irradiation chemotherapy followed by risk-adapted radiotherapy and maintenance chemotherapy. A total of 153 patients from the Polish Pediatric Neuro-Oncology Group were included in the analysis. The median age at diagnosis was 8.0 years, and median follow-up time was 6.4 years. Sixty-seven patients were classified as standard-risk and eighty-six as high-risk. Overall survival (OS) and event-free survival (EFS) for standard-risk patients at 5 years (±standard error) were 87 ± 4.3% and 84 ± 4.6%, respectively, while 5-year OS and EFS for high-risk patients were 81 ± 4.3% and 79 ± 4.5%, respectively. Only one patient had disease progression prior to radiotherapy. This study demonstrates promising survival outcomes in patients treated with pre-irradiation chemotherapy followed by risk-adapted CSI and adjuvant chemotherapy. Such an approach may be useful in cases where the initiation of radiotherapy may need to be delayed, a common occurrence in many institutions globally. Full article

Purpose: To report our design, manufacturing, commissioning and initial clinical experience with a table-mounted range shifter board (RSB) intended to replace the machine-mounted range shifter (MRS) in a synchrotron-based pencil beam scanning (PBS) system to reduce penumbra and normal tissue dose for image-guided pediatric craniospinal irradiation (CSI). Methods: A custom RSB was designed and manufactured from a 3.5 cm thick slab of polymethyl methacrylate (PMMA) to be placed directly under patients, on top of our existing couch top. The relative linear stopping power (RLSP) of the RSB was measured using a multi-layer ionization chamber, and output constancy was measured using an ion chamber. End-to-end tests were performed using the MRS and RSB approaches using an anthropomorphic phantom and radiochromic film measurements. Cone beam CT (CBCT) and 2D planar kV X-ray image quality were compared with and without the RSB present using image quality phantoms. CSI plans were produced using MRS and RSB approaches for two retrospective pediatric patients, and the resultant normal tissue doses were compared. Results: The RLSP of the RSB was found to be 1.163 and provided computed penumbra of 6.9 mm in the phantom compared to 11.8 mm using the MRS. Phantom measurements using the RSB demonstrated errors in output constancy, range, and penumbra of 0.3%, −0.8%, and 0.6 mm, respectively. The RSB reduced mean kidney and lung dose compared to the MRS by 57.7% and 46.3%, respectively. The RSB decreased mean CBCT image intensities by 86.8 HU but did not significantly impact CBCT or kV spatial resolution providing acceptable image quality for patient setup. Conclusions: A custom RSB for pediatric proton CSI was designed, manufactured, modeled in our TPS, and found to significantly reduce lateral proton beam penumbra compared to a standard MRS while maintaining CBCT and kV image-quality and is in routine use at our center. Full article

Craniospinal irradiation (CSI) is a complex radiation technique employed to treat patients with primitive neuroectodermal tumors such as medulloblastoma or germinative brain tumors with the risk of leptomeningeal spread. In adults, this technique poses a technically challenging planning process because of the complex shape and length of the target volume. Thus, it requires multiple fields and different isocenters to guarantee the primary-tumor dose delivery. Recently, some authors have proposed the use IMRT technique for this planning with the possibility of overlapping adjacent fields. The high-dose delivery complexity demands three-dimensional dosimetry (3DD) to verify this irradiation procedure and motivated this study. We used an optical CT and a radiochromic Fricke-xylenol-orange gel with the addition of formaldehyde (FXO-f) to evaluate the doses delivered at the field junction region of this treatment. We found 96.91% as the mean passing rate using the gamma analysis with 3%/2 mm criteria at the junction region. However, the concentration of fail points in a determined region called attention to this evaluation, indicating the advantages of employing a 3DD technique in complex dose-distribution verifications. Full article

Background: Embryonal tumors represent a heterogeneous entity of brain tumors that need a multidisciplinary treatment including cranio-spinal irradiation (CSI), with a known impact on the acute toxicity. Proton therapy (PT) boasts a reduction in acute hematological toxicity. Methods: We retrospectively examined 20 pediatric patients affected by high-risk medulloblastoma and other rare embryonal brain tumors subjected to CSI with PT from September 2016 to April 2020. Before CSI, all patients received induction chemotherapy, and three patients additionally received two high-dose courses with thiotepa, followed by an autologous haemopoietic stem cell transplantation. We recorded the total white blood cell count, absolute neutrophil count, platelets, and hemoglobin levels for all patients during PT. Results: Leucocytes and neutrophils decreased directly after the beginning of treatment, reaching a complete recovery at the end of treatment. Hemoglobin values remained constant over the treatment course. The median platelet value decreased until reaching a plateau around halfway through therapy, followed by a slow increase. No cases of febrile neutropenia or severe infections were reported. No treatment discontinuation due to hematological toxicity was necessary. Conclusions: CSI with PT was proven to be safe in this setting of pediatric patients. Our study showed that despite all patients having undergone chemotherapy prior to irradiation, no serious hematological toxicity was reported at the end of the treatment with PT, and, therefore, no treatment was discontinued or delayed. Full article

The role of cranio-spinal irradiation (CSI) for primary extraosseous intraspinal Ewing sarcoma (EwS) remains unclear. Here, we evaluate clinical and survival outcomes in patients with primary intraspinal EwS treated with CSI as part of multimodal primary therapy regimens. We abstracted patient information, including details on treatment application, efficacy, and tolerance from the literature and our hospital database for a cohort of 24 primary intraspinal EwS patients treated with CSI. Median age was 25.5 years, median CSI dose was 36 Gy and mean boost dose was 12.8 Gy. Sixteen patients (66.7%) achieved complete radiological remission, another 5 patients demonstrated partial response and 1 patient showed no response to treatment. Compared to a cohort of patients treated with focal radiotherapy, CSI patients were more likely to have multifocal disease at time of diagnosis (p = 0.001) and intradural tumor location (p < 0.001). Despite over-representation of these unfavorable characteristics, there was no survival difference between groups (p = 0.58). While CSI shows promising results in the treatment of primary intraspinal EwS, treatment should be considered individually based on tumor and patient characteristics in the absence of prospective trials. Full article

Medulloblastoma is the most frequent malignant brain tumor in children. During the last decades, the therapeutic landscape has changed significantly with craniospinal irradiation as the backbone of treatment. Survival times have increased and treatments were stratified according to clinical and later molecular risk factors. In this review, current evidence regarding the efficacy and toxicity of radiotherapy in medulloblastoma is summarized and discussed mainly based on data of controlled trials. Current concepts and future perspectives based on current risk classification are outlined. With the introduction of CSI, medulloblastoma has become a curable disease. Due to combination with chemotherapy, survival rates have increased significantly, allowing for a reduction in radiation dose and a decrease of toxicity in low- and standard-risk patients. Furthermore, modern radiotherapy techniques are able to avoid side effects in a fragile patient population. However, high-risk patients remain with relevant mortality and many patients still suffer from treatment related toxicity. Treatment needs to be continually refined with regard to more efficacious combinatorial treatment in the future. Full article

Objectives: Recent trials with craniospinal irradiation (CSI) via helical Tomotherapy (HT) demonstrated encouraging medulloblastoma results. In this study, we assess the toxicity profile of different radiation techniques and estimate survival rates. Materials and Methods: We reviewed the records of 46 patients who underwent irradiation for medulloblastoma between 1999 and 2019 (27 conventional radiotherapy technique (CRT) and 19 HT). Patient, tumor, and treatment characteristics, as well as treatment outcomes—local control rate (LCR), event-free survival (EFS), and overall survival (OS)—were reviewed. Acute and late adverse events (AEs) were evaluated according to the Radiation Therapy Oncology Group and the European Organization for Research and Treatment of Cancer (RTOG/EORTC) criteria. Results: In total, 43 courses of CSI and three local RT were administered to the 46 patients: 30 were male, the median age was 7 years (range 1–56). A median total RT dose of 55 Gy (range 44–68) and a median CSI dose of 35 Gy (range, 23.4–40) was delivered. During follow-up (median, 99 months), six patients (13%) developed recurrence. The EFS rate after 5 years was 84%. The overall OS rates after 5 and 10 years were 95% and 88%, respectively. There were no treatment-related deaths. Following HT, a trend towards lower grade 2/3 acute upper gastrointestinal (p = 0.07) and subacute CNS (p = 0.05) toxicity rates was detected compared to CRT-group. The risk of late CNS toxicities, mainly grade 2/3, was significantly lower following HT technique (p = 0.003). Conclusion: CSI via HT is an efficacious treatment modality in medulloblastoma patients. In all, we detected a reduced rate of several acute, subacute, and chronic toxicities following HT compared to CRT. Full article

Introduction: Due to the rarity of nongerminomatous germ cell tumors (NGGCT) with non-standard treatment as yet, we report retrospectively our 30 year experience with chemotherapy followed by craniospinal irradiation (CSI), plus a boost of whole ventricular irradiation (WVI)/tumor bed (TB), tailored to pre-radiation chemotherapy response. Methods: Between 1988 and 2016, 28 patients received four cycles of PEB (cisplatin/etoposide/bleomycin), then CSI, and two further PEB cycles. Between 1988 and1994, CSI was 25.5 Gy for patients in complete remission (CR), 30 Gy if in partial remission (PR) or metastatic, with a boost to TB up to 45–54 Gy. In the period of 1995–2010, the boost included WVI and any extra-ventricular tumor sites up to 45 Gy. After 2010, CSI was reduced to 25.5 Gy for all non-metastatic patients, and a boost was given only to TB up to 40.5/45.5 Gy, depending on patients’ CR/PR status. After 2003, patients with alfafetoprotein (αFP) > 1000 ng/mL received intensified treatment, also including autologous stem cell transplantation. Results: Among 28 patients (23 males; median age 12 years, 6 metastatic), 25 responded to PEB, and three progressed (PD) after one to four cycles; 26 received radiotherapy obtaining 13 CR, 7 PR and 5 stable disease (SD), 1 PD; 6 (21%) died (5 for disease, 1 for pneumonia while in CR). Five-year overall survival (OS) and progression-free survival (PFS) were both 81%; 10 year OS and PFS 81% and 76%, respectively (median follow-up 11 years). Conclusions: Survival for children with NGGCT, independently from disease extent, was encouraging. Further studies should elucidate which patients could benefit from reduced volume and dose irradiation. Full article

Suprasellar germ cell tumors (S-GCTs) are rare, presenting in either solitary or multifocal fashion. In this study, we retrospectively examine 22 solitary S-GCTs and 20 bifocal germ cell tumors (GCTs) over a 30-year period and demonstrate clinical, radiographic, and prognostic differences between the two groups with therapeutic implications. Compared to S-GCTs, bifocal tumors were almost exclusively male, exhibited higher rate of metastasis, and had worse rates of progression free and overall survival trending toward significance. We also introduce a novel magnetic resonance (MR) imaging classification of suprasellar GCT into five types: a IIIrd ventricle floor tumor extending dorsally with or without an identifiable pituitary stalk (Type Ia, Ib), ventrally (Type III), in both directions (Type II), small lesions at the IIIrd ventricle floor extending to the stalk (Type IV), and tumor localized in the stalk (Type V). S-GCTs almost uniformly presented as Type I–III, while most bifocal GCTs were Type IV with a larger pineal mass. These differences are significant as bifocal GCTs representing concurrent primaries or subependymal extension may be treated with whole ventricle radiation, while cerebrospinal fluid (CSF)-borne metastases warrant craniospinal irradiation (CSI). Although further study is necessary, we recommend CSI for bifocal GCTs exhibiting high-risk features such as metastasis or non-germinomatous germ cell tumor histology. Full article

Medulloblastoma is an embryonal tumor that shows a predilection for distant metastatic spread and leptomeningeal seeding. For most patients, optimal management of medulloblastoma includes maximum safe resection followed by adjuvant craniospinal irradiation (CSI) and chemotherapy. Although CSI is crucial in treating medulloblastoma, the realization that medulloblastoma is a heterogeneous disease comprising four distinct molecular subgroups (wingless [WNT], sonic hedgehog [SHH], Group 3 [G3], and Group 4 [G4]) with distinct clinical characteristics and prognoses has refocused efforts to better define the optimal role of CSI within and across disease subgroups. The ability to deliver clinically relevant CSI to preclinical models of medulloblastoma offers the potential to study radiation dose and volume effects on tumor control and toxicity in these subgroups and to identify subgroup-specific combination adjuvant therapies. Recent efforts have employed commercial image-guided small animal irradiation systems as well as custom approaches to deliver accurate and reproducible fractionated CSI in various preclinical models of medulloblastoma. Here, we provide an overview of the current clinical indications for, and technical aspects of, irradiation of pediatric medulloblastoma. We then review the current literature on preclinical modeling of and treatment interventions for medulloblastoma and conclude with a summary of challenges in the field of preclinical modeling of CSI for the treatment of leptomeningeal seeding tumors. Full article

With robust optimization for spot scanning proton therapy now commercially available, the ability exists to account for setup, range, and interfield uncertainties during optimization. Robust optimization is particularly beneficial for craniospinal irradiation (CSI) where the large target volume lends itself to larger setup uncertainties and the need for robust match lines can all be handled with the uncertainty parameters found inside the optimizer. Suggested robust optimization settings, parameters, and image guidance for CSI patients using proton therapy spot scanning are provided. Useful structures are defined and described. Suggestions are given for perturbations to be entered into the optimizer in order to achieve a plan that provides robust target volume coverage and critical structure sparing as well as a robust match line. Interfield offset effects, a concern when using multifield optimization, can also be addressed within the robust optimizer. A robust optimizer can successfully be employed to produce robust match lines, target volume coverage, and critical structure sparing under specified uncertainties. The robust optimizer can also be used to reduce effects arising from interfield uncertainties. Using robust optimization, a plan robust against setup, range, and interfield uncertainties for craniospinal treatments can be created. Utilizing robust optimization allows one to ensure critical structures are spared and target volumes are covered under the desired uncertainty parameters. Full article