Successful Implementation of Image-Guided Pencil-Beam Scanning Proton Therapy in Medulloblastomas.

Medulloblastoma is the most common malignant brain tumour in children, while much rarer in adults. Although the prognosis and outcomes have greatly improved in the era of modern multidisciplinary management, long-term treatment-induced toxicities are common. Craniospinal irradiation followed by a boost to the primary and metastatic tumour sites forms the backbone of treatment. Proton therapy has been endorsed over conventional photon-based radiotherapy due to its superior dosimetric advantages and subsequently lower incidence and severity of toxicities. We report here our experience from South-East Asia's first proton therapy centre of treating 40 patients with medulloblastoma (38 children and adolescents, 2 adults) who received image-guided, intensity-modulated proton therapy with pencil-beam scanning between 2019 and 2023, with a focus on dosimetry, acute toxicities, and early survival outcomes. All patients could complete the planned course of proton therapy, with mostly mild acute toxicities that were manageable on an outpatient basis. Haematological toxicity was not dose-limiting and did not prolong the overall treatment time. Preliminary data on early outcomes including overall survival and disease-free survival are encouraging, although a longer follow-up and data on long-term toxicities are needed.

Comparison of dosimetric analysis of organs at risk and target volumes for ovoids and cylinders in endometrial carcinoma.

Purpose: To compare dose volume parameters of target and organs at risk in vaginal vault brachytherapy using ovoids or cylinder in post-operative endometrial carcinoma. Material and methods: The study was done among 25 histologically proven post-operative endometrial carcinoma patients requiring vaginal brachytherapy. All patients underwent both cylinder and ovoids application alternatively on weekly basis. Ovoids size ranged from 2 to 3 cm diameter. Diameters of cylinder ranged between 2.5 and 3.5 cm. Bladder, rectum, urethra, and clinical target volume (CTV) were contoured on CT simulation images. Prescribed dose was 6-7 Gy in 2-3 fractions at 0.5 cm from the surface of applicator. Results: The mean values of D90, D50, V150, V100, V90, and V50 of CTV were comparable between cylinder and ovoids plans. The mean dose of CTV was significantly higher with cylinder than with ovoids, and D100 was significantly higher with ovoids (mean = 15.63 Gy vs. 14.64 Gy, p = 0.016, and D100 = 37.82% vs. 42.86%, p = 0.042, for cylinder vs. ovoids). In the dosimetry of the vault, D90, D50, V100, V90, V50, and mean of the vault did not show any significant difference between cylinder and ovoids. The V150 was significantly higher with cylinder plans than ovoids, and D100 of the vault was significantly higher with ovoids plans (V150 = 14.81% vs. 6.86%, p = 0.02, and D100 = 37.77% vs. 44.80%, p = 0.029, for cylinder vs. ovoids). D0.1cc, D1cc, D2cc, and mean for the bladder, rectum, and urethra were comparable between the cylinder and ovoid plans. Conclusions: The present study showed that the dose to organs at risk, most of the dosimetric parameters of CTV, and vault were comparable between the cylinder and ovoid plans. Both applicators provide good reproducibility. The choice of applicator will ultimately depend on the institutional policies and oncologist decision. However, in patients with dog-ear configuration of the vagina, ovoids may be preferred as per ABS guidelines.

Diffuse intrinsic pontine gliomas in adults: A retrospective study.

Background: Brainstem gliomas (BSG) constitutes very small proportion in adults brain tumors with pons as most common location. There is significant paucity in literature for adult diffuse intrinsic pontine gliomas (DIPG). Objective: In this study, we attempt to review the outcomes of DIPG in single institute. Methods: We performed a retrospective chart review of adult DIPG from last 8 years (2010-2018) in a tertiary institute. DIPG was defined as expansile lesions involving more than 50% of the greatest diameter in the pons. Results: We found a total 46 patients with the diagnosis of adult BSG. Based on the definition, 23 patients with adult DIPG qualified to be included in the study. The median age was 32 years (IQR: 22-41), with a sex ratio of 16/7 (M/F). Cranial palsies were found in 17 (73%) patients. The median duration of symptoms was 6 months. On magnetic resonance imaging (MRI), contrast enhancement was found in seven (30%) patients. Biopsy was done in five patients. Median follow up was 11 months (IQR: 7-15). Median overall survival (OS) was 15 months (95%, CI 8.3-21.6). Fourteen patients had succumbed to death at the latest follow-up, and seven patients were alive. Median OS for the patients with age less than 40 years and more than 40 years was 7 and 22 months, respectively (p = 0.016). Rest of the variables did not effect OS significantly. Conclusion: Adult DIPG's significantly differs from pediatric counterparts in clinical characteristics, as well as OS. Age was the only factor which was significantly associated with survival in our study. Long-term studies with molecular profiling may help in further characterizing these lesions.

Combined amino acid PET-MRI for identifying recurrence in post-treatment gliomas: together we grow.

PURPOSE: The aim of this study is to compare the diagnostic accuracy of amino acid PET, MR perfusion and diffusion as stand-alone modalities and in combination in identifying recurrence in post-treatment gliomas and to qualitatively assess spatial concordance between the three modalities using simultaneous PET-MR acquisition. METHODS: A retrospective review of 48 cases of post-treatment gliomas who underwent simultaneous PET-MRI using C11 methionine as radiotracer was performed. MR perfusion and diffusion sequences were acquired during the PET study. The following parameters were obtained: TBRmax, TBRmean, SUVmax, and SUVmean from the PET images; rCBV from perfusion; and ADCmean and ADCratio from the diffusion images. The final diagnosis was based on clinical/imaging follow-up and histopathology when available. ROC curve analysis in combination with logistic regression analysis was used to compare the diagnostic performance. Spatial concordance between modalities was graded as 0, 1, and 2 representing discordance, < 50% and > 50% concordance respectively. RESULTS: There were 35 cases of recurrence and 13 cases of post-treatment changes without recurrence. The highest area under curve (AUC) was obtained for TBRmax followed by rCBV and ADCratio. The AUC increased significantly with a combination of rCBV and TBRmax. Amino acid PET showed the highest diagnostic accuracy and maximum agreement with the final diagnosis. There was discordance between ADC and PET in 22.9%, between rCBV and PET in 16.7% and between PET and contrast enhancement in 14.6% cases. CONCLUSION: Amino acid PET had the highest diagnostic accuracy in identifying recurrence in post-treatment gliomas. Combination of PET with MRI further increased the AUC thus improving the diagnostic performance.

Rhabdoid meningiomas: Clinicopathological analysis of a rare variant of meningioma.

INTRODUCTION: Rhabdoid Meningiomas (RM) are rare malignant type of meningiomas, classified as grade III in the WHO classification. Only a few case series have been reported, and factors affecting prognosis are still unclear. METHODS: We did a retrospective chart review of all the RMs diagnosed in our institute between 2007 and 2019. Demographic profile, clinical status, imaging, surgical procedures used, post-operative course, adjuvant therapy and follow-ups were reviewed. Histopathological slides were also reviewed. RESULTS: There were 11 patients with RM who underwent 17 surgical procedures between them. Median age was 26 years. On imaging, four had lesions in skull base, three in convexity and four in parasagittal region. Five patients had lesions which had bled and two had leptomeningeal dissemination. Two patients underwent Simpson's grade 1 excision, seven underwent grade 2 and one patient each underwent grade 3 and 5 excisions. One patient presented with poor sensorium and underwent surgery but ultimately succumbed. All reported patients had Rhabdoid features (>50%). Features of anaplasia were seen in four cases and atypical meningioma in others. The median progression-free-survival and overall survival was 6 months and 9 months, respectively. Female gender (n = 5; p = 0.032) and patients who received radiotherapy (p = 0.030) had a survival advantage. Location of the tumor (p = 0.43), presence of hemorrhage in the lesion (p = 0.49), grade of excision (p = 0.40) and WHO pathological grade (p = 0.11) did not have a statistically significant survival benefit. CONCLUSION: Female gender and adjuvant radiotherapy were associated with survival advantage in our sample. Large studies are required to establish the factors associated with survival.

Hippocampal radiotherapy dose constraints for predicting long-term neurocognitive outcomes: mature data from a prospective trial in young patients with brain tumors.

BACKGROUND: Hippocampus is considered to be the seat for neurocognitive functions. Avoidance of hippocampus during radiotherapy to brain may serve to preserve various domains of neurocognition. We aimed to derive radiotherapy dose constraints to hippocampi for preserving neurocognition in young patients with brain tumors by measuring various neurocognitive parameters. METHODS: Forty-eight patients with residual/progressive benign or low-grade brain tumors treated with stereotactic conformal radiotherapy (SCRT) to a dose of 54 Gy in 30 fractions underwent prospective neuropsychological assessments at baseline before SCRT and at 6 months and 2, 3, 4, and 5 years. Hippocampi were drawn as per the Radiation Therapy Oncology Group atlas. Longitudinal change in intelligence quotient scores was correlated with hippocampal doses. RESULTS: Mean volume of bilateral hippocampi was 4.35 cc (range: 2.12-8.41 cc). Craniopharyngioma was the commonest histologic subtype. A drop of >10% in mean full-scale intelligence quotient (FSIQ) scores at 3 and 5 years post SCRT was observed in patients in whom left hippocampus received a mean dose of 30.7 Gy (P = 0.04) and 31 Gy (P = 0.04), respectively. Mean performance quotient (PQ) scores dropped > 10% at 5 years when the left hippocampus received a dose of > 32 Gy (P = 0.03). There was no significant correlation of radiotherapy doses with verbal quotient, or with doses received by the right hippocampus. Multivariate analysis revealed young age (<13 y) and left hippocampus dose predicted for clinically relevant decline in certain neurocognitive domains. CONCLUSIONS: A mean dose of ≤30 Gy to the left hippocampus as a dose constraint for preserving intelligence quotient is suggested. KEY POINTS: 1. Children and young adults with benign and low-grade gliomas survive long after therapy.2. Higher dose to the hippocampi may result in long-term neurocognitive impairment.3. Mean dose of <30 Gy to left hippocampus could be used as a pragmatic dose constraint to prevent long-term neurocognitive decline.

Dose-Constraint Model to Predict Neuroendocrine Dysfunction in Young Patients With Brain Tumors: Data From a Prospective Study.

PURPOSE: We report on a possible dose-constraint model to predict long-term neuroendocrine dysfunction after cranial irradiation in children and young adults with benign and low-grade brain tumors treated with stereotactic conformal radiation therapy (RT) in a prospective clinical trial. METHODS AND MATERIALS: Patients treated with stereotactic conformal RT (54 Gy in 30 fractions) were included for analysis if their co-registered planning computed tomography and magnetic resonance imaging scans were available, along with baseline and post-RT endocrine assessment for at least 2 years. The hypothalamus-pituitary axis (HPA) was contoured on the fused computed tomography-magnetic resonance imaging data set. Worsening of endocrine function was defined biochemically as a new onset endocrine deficit or worsening of preexisting endocrine deficit. Dosimetric indices of HPA, extracted using cumulative dose-volume histograms, were correlated with worsening endocrine function using logistic regression analysis. RESULTS: A total of 51 patients (median age: 13 years; range, 5-25 years) were included. Worsening post-RT endocrine levels were seen in 27 of 51 patients (47%). Growth hormone was the most commonly affected (70%), followed by cortisol (44%), gonadotropin (40%), and thyroxine (7%). The mean of the maximum and minimum doses to HPA was 42.1 Gy and 35.7 Gy, respectively. For patients with worsening endocrine levels, the mean maximum dose to HPA was 46.6 Gy compared with 36.5 Gy in patients with stable functions. The mean minimum dose to HPA was also higher (40.5 Gy vs 29.6 Gy) in patients with endocrine dysfunction. Logistic regression analysis identified the volume of HPA receiving 50% of the prescribed dose as the only statistically significant parameter predicting endocrine dysfunction. A dose of ≥27 Gy to any volume of HPA was associated with a 4-fold increase in risk of endocrine dysfunction (odds ratio: 4.05; 95% confidence interval, 1.07-15.62; P = .038). CONCLUSIONS: Our prospective longitudinal study demonstrates the feasibility of HPA avoidance using modern, high-precision, conformal RT techniques and correlates HPA dosimetry with neuroendocrine dysfunction. We suggest restricting HPA doses to <27 Gy to minimize the risk of post-RT neuroendocrine deficits.

Efficacy of Stereotactic Conformal Radiotherapy vs Conventional Radiotherapy on Benign and Low-Grade Brain Tumors: A Randomized Clinical Trial.

IMPORTANCE: Evidence for application of stereotactic and other conformal radiotherapy techniques in treating brain tumors is largely based on data derived from dosimetric, retrospective, or small prospective studies. Therefore, we conducted a randomized clinical trial of stereotactic conformal radiotherapy (SCRT) compared with conventional radiotherapy (ConvRT) evaluating clinically meaningful end points. OBJECTIVE: To compare neurocognitive and endocrine functional outcomes and survival at 5 years in young patients with residual and/or progressive benign or low-grade brain tumors treated with SCRT and ConvRT techniques. DESIGN, SETTING, AND PARTICIPANTS: This phase 3 randomized clinical trial enrolled 200 young patients (ages 3-25 years) with residual or progressive benign or low-grade brain tumors at a single center between April 2001 to March 2012. Patients were randomly allocated (1:1) to either SCRT (n = 104) or ConvRT (n = 96) arms. INTERVENTIONS: Patients were randomly assigned to either high-precision SCRT or ConvRT to a dose of 54 Gy in 30 fractions over 6 weeks. MAIN OUTCOMES AND MEASURES: Detailed neuropsychological and neuroendocrine assessments were performed at preradiotherapy baseline, at 6 months, and annually thereafter until 5 years on longitudinal follow-up. Change in these functional parameters was compared between the 2 arms as the primary end point and overall survival (OS) as the secondary end point. RESULTS: In total, 200 young patients (median [interquartile range] age, 13 [9-17] years; 133 males and 67 females) were enrolled. Mean full-scale or global intelligence quotient (IQ) and performance IQ scores over a period of 5 years were significantly superior in patients treated with SCRT compared with those treated with ConvRT (difference in slope = 1.48; P = .04 vs difference in slope = 1.64; P = .046, respectively). Cumulative incidence of developing new neuroendocrine dysfunction at 5 years was significantly lower in patients treated with SCRT compared with ConvRT (31% vs 51%; P = .01) while developing a new neuroendocrine axis dysfunction in patients with preexisting dysfunction in at least 1 axis at baseline was also significantly lower in the SCRT arm compared with the ConvRT arm (29% vs 52%; P = .02). Five-year OS in SCRT and ConvRT arms was 86% and 91%, respectively (P = .54). CONCLUSIONS AND RELEVANCE: In young patients with residual and/or progressive benign or low-grade brain tumors requiring radiotherapy for long-term tumor control, SCRT compared with ConvRT achieves superior neurocognitive and neuroendocrine functional outcomes over 5 years without compromising survival. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00517959.