Co-relation of Portal Vein Tumour Thrombus Response With Survival Function Following Robotic Radiosurgery in Vascular Invasive Hepatocellular Carcinoma.

Background/aims: The aim of this study was to prospectively evaluate stereotactic body radiotherapy (SBRT) with robotic radiosurgery in hepatocellular carcinoma patients with macrovascular invasion (HCC-PVT). Materials and methods: Patients with inoperable HCC-PVT, good performance score (PS0-1) and preserved liver function [up to Child-Pugh (CP) B7] were accrued after ethical and scientific committee approval [Clinical trial registry-India (CTRI): 2022/01/050234] for treatment on robotic radiosurgery (M6) and planned with Multiplan (iDMS V2.0). Triple-phase contrast computed tomography (CT) scan was performed for contouring, and gross tumour volume (GTV) included contrast-enhancing mass within main portal vein and adjacent parenchymal disease. Dose prescription was as per risk stratification protocol (22-50 Gy in 5 fractions) while achieving the constraints of mean liver dose <15 Gy, 800 cc liver <8 Gy and the duodenum max of <24 Gy). Response assessment was done at 2 months' follow-up for recanalization. Patient- and treatment-related factors were evaluated for influence in survival function. Results: Between Jan 2017 and May 2022, 318 consecutive HCC with PVT patients were screened and 219 patients were accrued [male 92%, CP score: 5-7 90%, mean age: 63 years (38-85 yrs), Cancer of the Liver Italian Program <3: 84 (40%), 3-6117 (56%), infective aetiology 9.5%, performance status (PS): 0-37%; 1-56%]. Among 209 consecutive patients accrued for SBRT treatment (10 patients were excluded after accrual due to ascites and decompensation), 139 were evaluable for response assessment (>2 mo follow-up). At mean follow-up of 12.21 months (standard deviation: 10.66), 88 (63%) patients expired and 51 (36%) were alive. Eighty-two (59%) patients had recanalization of PVT (response), 57 (41%) patients did not recanalize and 28 (17%) had progressive/metastatic disease prior to response evaluation (<2 months). Mean overall survival (OS) in responders and non-responders were 18.4 [standard error (SE): 2.52] and 9.34 month (SE 0.81), respectively (P < 0.001). Mean survival in patients with PS0, PS1 and PS2 were 17, 11.7 and 9.7 months (P = 0.019), respectively. OS in partial recanalization, bland thrombus and complete recanalization was 12.4, 14.1 and 30.3 months, respectively (P-0.002). Adjuvant sorafenib, Barcelona Clinic Liver Classification stage, gender, age and RT dose did not influence response to treatment. Recanalization rate was higher in good PS patients (P-0.019). OS in patients with response to treatment, in those with no response to treatment, in those who are fit but not accrued and in those who are not suitable were 18.4, 9.34, 5.9 and 2.6 months, respectively (P-<0.001). Thirty-six of 139 patients (24%) had radiation-induced liver disease (RILD) [10 (7.2%) had classic RILD & 26 (19%) had non-classic RILD]. Derangement in CP score (CP score change) by more than 2 was seen in 30 (24%) within 2-month period after robotic radiosurgery. Eighteen (13%) had unplanned admissions, two patients required embolization due to fiducial-related bleeding and 20 (14%) had ascites, of which 9 (6%) patients required abdominocentesis. Conclusion: PVT response or recanalization after SBRT is a statistically significant prognostic factor for survival function in HCC-PVT.

Validation of Combs prognostic scoring system in Indian recurrent glioma patients treated with re-radiation.

PURPOSE: Retrospective audit of recurrent glioma patients treated by different fractionation schedules and to validate the modified Combs prognostic score in Indian patient cohort. MATERIALS AND METHODS: Between Jan 2009 and June 2022, 66 recurrent gliomas patients treated with standard adjuvant treatment-radiation (RT) ± temozolomide (chemotherapy)-and re-treated with RT (±chemotherapy) were categorized as per modified Combs prognostic criteria and outcomes were compared. RESULTS: Sixty-six patients with recurrent gliomas who received reirradiation (re-RT) were audited-53% males; 61% Karnofsky performance status (KPS) ≥80 at time of re-RT; median age 41.5 years (range, 6 to 70 years); 67% <50 years; primary histology low-grade glioma in 33% ; grade III 27%, grade IV 40%; initial median dose of 60 Gy equivalent dose in 2 Gy fractions EQD2; maximum safe resection at recurrence 41%; mean and median follow-up 78 ± 51 months and 66 months. Mean time interval between RT was 46.4 ± 39 months. Mean planning target volume (PTV) volume in conventional RT (Conv-RT), hypofractionated RT (Hypo-RT), and ultra-hypofractionated RT (UF-RT) was 226.1 ± 140.7 mL, 162.8 ± 123.3 mL, and 143.3 ± 145.8 mL. Mean dose for Conv-RT, Hypo-RT, and UF-RT was 50 Gy (range, 40 to 60), 31 Gy (range, 20 to 40), and 20 Gy (range, 10 to 30). Mean overall survival (OS) in Conv-RT, Hypo-RT, and UF-RT cohort was 18.8 months (range, 2.4 to 76.8); 6.6 months (range, 2 to 17.4), and 13.9 months (range, 3 to 131.9). Median OS as per Combs criteria were 16.6 months (Group a), 24.6 months (Group b), 4.6 months (Group c), and 3 months (Group d). Significant survival benefit was with good KPS score (KPS >80 vs. <80; 20.46 vs. 5.25 months; p < 0.001), patients receiving salvage chemotherapy (20.46 vs. 6.96 months; p = 0.001), and patients received re-RT biological equivalent dose BED3 >80 Gy (16.62 vs. 5.48 months; p = 0.03). Median OS in our patient cohort and Combs cohort in Group a was 16.6 and 19.5 months; Group b was 24.6 and 11.3 months; Group c was 4.7 and 8.1 months, and Group d was 2 and 5.5 months, respectively. Six months survival in our patient cohort and Combs cohort in Groups a, b, c, d were 100%, 92%, 34%, 17% and 94%, 79%, 70%, 41%, respectively. Twelve months survival in our patient cohort and Combs cohort in Groups a, b, c, d were 88%, 74%, 22%, 0% and 88%, 47%, 22%, 7%, respectively. CONCLUSION: Modified Combs prognostic factors predicts OS and is applicable in Indian subcontinent patient population.

Efficacy of memantine in preventing neurocognitive dysfunction induced by radiation therapy in patients with brain metastases: A systematic review of clinical trials.

PURPOSE: About 50%-90% of patients with brain metastases who receive radiation therapy experience cognitive impairment. This systematic review aims to gather credible sources of comprehensive information on the efficacy of memantine in preventing cognitive dysfunction. METHODS: A comprehensive review conducted in compliance with the PRISMA statement and systematic search was performed across five databases included PubMedⓇ, EmbaseⓇ, ScopusⓇ, Cochrane LibraryⓇ, and ClinicalTrial.gov.in from inception until November 2021. RESULTS: A total of four eligible studies were selected in this review that included 1,444 patients with brain metastases who received radiation therapy (Intervention group [n = 729] and control group [n = 715]). Overall, three of the four studies reported some improvement in neurocognitive function in at least one or more parameters such as recall and recognition (P = .39, P = .10 and P = .05), verbal fluency (P = .03 and P < .0001), complex attention (P = .59) executive function (P = .92) and normal appearing white matter (P = .01) following memantine therapy compared to control group. Further, two of the four studies reported an improvement in the patients' quality of life following memantine therapy compared to the control group, and there was no significant difference in the toxicity profile of the interventional compared to the control group as reported from two studies. CONCLUSION: This review embraces the comprehensive evidence that the use of memantine therapy in patients with brain metastases to prevent radiation-induced neurocognitive dysfunction has a modest and statistically significant beneficial impact in improving quality of life and preserving some neurocognitive function without any complications. Pending the completion of additional ongoing studies, one can argue that memantine is a reasonable treatment to consider in patients with brain metastases while they receive whole brain radiation therapy.

Preservation of cognitive function after brain irradiation.

OBJECTIVE: Approximately 50-90% of brain metastatic patients who receive radiation therapy (RT) exhibit cognitive decline which may affects the quality of life of cancer survivors. Hence preservation of cognitive functions in brain metastatic patients becomes important. This review aims to evaluates the pathology or mechanism of cognitive function impairment after brain irradiation and strategies available to preserve cognitive function after radiation therapy. DATA SOURCES: Published articles evaluating the pathology behind radiation induced cognitive impairment and strategies to resolve or preserve cognitive impairment were searched for in scientific databases (eg: PubMed, Scopus, Cochrane database, Google scholar) using keywords including memantine, brain metastases, radiation therapy, pathophysiology, pathogenesis, mechanism and prevention. DATA SUMMARY: Several hypotheses have been offered to explain the mechanism of radiation induced cognitive decline. Among them, vascular hypotheses play a significant role. Some pharmacological agents have been also tested in patients receiving radiotherapy, memantine was found beneficial based with the reference to existing data. CONCLUSION: Future studies are required to evaluate the impact of memantine in different types of radiation therapy procedures and its effects on quality of life of brain metastatic survivors.

Tackling a recurrent pinealoblastoma.

Pineoblastomas are rare, malignant, pineal region lesions that account for <0.1% of all intracranial tumors and can metastasize along the neuroaxis. Pineoblastomas are more common in children than in adults and adults account for <10% of patients. The management of pinealoblastoma is multimodality approach, surgery followed with radiation and chemotherapy. In view of aggressive nature few centres use high dose chemotherapy with autologus stem cell transplant in newly diagnosed cases but in recurrent setting the literature is very sparse. The present case represents the management of pinealoblastoma in the recurrent setting with reirradiation and adjuvant carmustine chemotherapy wherein the management guidelines are not definitive.