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.

Extramedullary plasmacytoma of the larynx - Case report.

Extramedullary plasmacytoma of the larynx is an extremely rare entity accounting for 0.04-0.45% of malignant tumours of the larynx. The objective of this clinical case report is to highlight the diagnosis and management of a unique case such as this. A 77-year-old gentleman presented with complaints of hoarseness for 1 year. Computed tomography image revealed a soft tissue mass lesion involving the right true vocal cord. Direct laryngoscopic biopsy was performed and subjected to histopathological examination, which showed collection of plasma cells. Immunohistochemistry confirmed the presence of Kappa and Lambda cells. Multiple myeloma (MM) was ruled out. The patient received radical intent radiation therapy using 3DCRT technique with a dose of 50Gy in 25# over 5 weeks. He experienced improvement in hoarseness on subsequent follow-up visits. At 1-year follow up, positron emission tomography computed tomography showed near total resolution of disease with no progression to MM. Radiation therapy alone is known to achieve good local control, recurrence free survival, and organ preservation in such cases.

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.

2023 Update of Indian National Association for Study of the Liver Consensus on Management of Intermediate and Advanced Hepatocellular Carcinoma: The Puri III Recommendations.

Hepatocellular carcinoma (HCC) presents significant treatment challenges despite considerable advancements in its management. The Indian National Association for the Study of the Liver (INASL) first published its guidelines to aid healthcare professionals in the diagnosis and treatment of HCC in 2014. These guidelines were subsequently updated in 2019. However, INASL has recognized the need to revise its guidelines in 2023 due to recent rapid advancements in the diagnosis and management of HCC, particularly for intermediate and advanced stages. The aim is to provide healthcare professionals with evidence-based recommendations tailored to the Indian context. To accomplish this, a task force was formed, and a two-day round table discussion was held in Puri, Odisha. During this event, experts in their respective fields deliberated and finalized consensus statements to develop these updated guidelines. The 2023 INASL guidelines offer a comprehensive framework for the diagnosis, staging, and management of intermediate and advanced HCC in India. They represent a significant step forward in standardizing clinical practices nationwide, with the primary objective of ensuring that patients with HCC receive the best possible care based on the latest evidence. The guidelines cover various topics related to intermediate and advanced HCC, including biomarkers of aggressive behavior, staging, treatment options, and follow-up care.

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.

Prospective Evaluation of Response to Treatment, Survival Functions, Recurrence Pattern and Toxicity Profile in Indian Patients with Oligo-Brain Metastasis Treated with Only SRS.

Background: Prospective analysis of oligo-brain metastasis in Indian patients treated with SRS-only treatment. Methods: Between January 2017 and May 2022, 235 patients were screened and 138 histologically proven and radiologically confirmed. One to five brain metastasis patients aged more than 18 years with good Karnofsky performance status (KPS >70) accrued in ethical and scientific committee-approved prospective observational study protocol for treatment with only radiosurgery (SRS) with robotic radiosurgery (CyberKnife, CK) [AIMS IRB: 2020-071; CTRI No: REF/2022/01/050237]. Immobilization was performed with a thermoplastic mask, contrast CT simulation was performed with 0.625 mm slices, fused with T1 contrast/T2 FLAIR MRI images for contouring. Planning target volume (PTV) margin of 2-3 mm and a dose of 20-30 Gy in 1-5 fractions. Response to treatment, new brain lesions free survival, overall survival, and toxicity profile after CK were evaluated. Results: In total,: 138 patients with 251 lesions were accrued (median age 59 years (interquartile range [IQR] 49-67 years; female 51%; headache in 34%, motor deficit in 7%, KPS >90 in 56%; lung primary in 44%, breast in 30%; oligo-recurrence in 45%; synchronous oligo-metastases in 33%; adenocarcinoma primary in 83%). One hundred seven patients (77%) received upfront Stereotactic radiotherapy (SRS), 15 (11%) received postoperative SRS, 12 (9%) received whole brain radiotherapy (WBRT) before SRS, and 3 (2%) received WBRT plus SRS boost. The majority had solitary (56%) brain metastasis, 28% had two to three lesions, and 16% had four to five brain lesions. Frontal (39%) was the most common site. Median PTV was 15.5 mL (IQR - 8.1-28.5 mL). Seventy-one (52%) patients were treated with single fractions, 14% with three, and 33% with five fractions. Fraction schedules were 20-2 4 Gy/1fr; 27 Gy/3fr, and 25 Gy/5 fractions (mean BED 74.6 Gy [SD ± 48.1; mean MU 16608], mean treatment time was 49 min (range 17-118 min]. Twelve Gy normal brain volume was 40.8 mL (3.2%) (range 19.3-73.7 mL). At a mean follow-up of 15 months (SD 11.9 months; max 56 months), the mean actuarial OS after SRS-only treatment was 23.7 months (95% confidence interval [CI] 20-28). Further 124 (90%) patients had >3 months, 108 (78%) had >6 months, 65 (47%) had >12 months, and 26 (19%) had >24 months follow-up. Intracranial disease and extracranial disease were controlled in 72 (52.2%) and 60 (43.5%), respectively. "In-field" recurrence, "out-of-field," and "both in and out-of-field" recurrences were in 11%, 42%, and 46%, respectively. At the last follow-up, 55 patients (40%) were alive, 75 (54%) died due to disease progression, and the status of 8 (6%) patients was not known. Among 75 patients who died, 46 (61%) had extracranial disease progression, 12 (16%) had only intracranial progression, and 8 (11%) had unrelated causes. Also, 12/117 (9%) had radiological confirmation of radiation necrosis. Prognostication based on western patients (primary tumor type, number of lesions extracranial disease) showed similar outcomes. Conclusions: SRS alone in brain metastasis is feasible in the Indian subcontinent with similar survival outcomes, recurrence patterns, and toxicity as published in the western literature. Patient selection, dose schedule, and planning need to be standardized to have similar outcomes. WBRT can be safely omitted in Indian patients with oligo-brain metastasis. Western prognostication nomogram is applicable in the Indian patient population.

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.

Hepatocellular carcinoma patients with portal vein thrombosis treated with robotic radiosurgery: Interim results of a prospective study.

BACKGROUND: This is a prospective study evaluating the role of stereotactic body radiotherapy (SBRT) with CyberKnife (CK) in Indian patients suffering from hepatocellular carcinoma with portal vein thrombosis (HCC-PVT). METHODS: Patients with inoperable HCC-PVT, good performance score (PS), and liver function are accrued for treatment on CK (version M6) and planned with Multiplan (iDMS V2.0). Triple-phase contrast computed tomography (CT) scan was done for contouring, and the gross tumor 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). RESULTS: Seventy-two HCC-PVT accrued till date (mean age 63 years [38-76 years], 96% male; Child-Pugh [CP] A 84%, B 9%; Barcelona-Clinic Liver Cancer [BCLC] C 96%; PS0-1: 80%, Karnofsky performance score [KPS]>70: 88%; co-morbidities 42%; infective 12%, alcohol intake 31%, adjuvant sorafenib 39%). CP scores 5, 6, 7, and 8 were in 35%, 32%, 8%, and 18%, respectively. Focal disease with portal vein thrombus (PVT) in 21%, liver involvement >50% and <50% in 46% and 32%. Liver cancer study group of Japan staging-based portal vein invasion VP2, VP3, and VP4 in 22%, 29%, and 40%. Cancer of the Liver Italian Programm (CLIP) scores 1, 2, 3, 4, and 5 were in 8%, 26%, 31%, 26%, and 7%, respectively. Mean follow-up was 7.3 months (median 6 months, standard deviation [SD] 6; range 3-30 months). Mean actuarial overall survival (OS) was 11.4 months (SE 1.587; 95% CI: 8-14.2 months). Six months and 12 months actuarial OS 55% and 38%, respectively. At last follow-up, 25/69 (36%) were alive and 44/69 (64%) were dead. Among 54 patients evaluated for response assessment, 23 (30%) had radiological confirmed PVT response, 1 (3%) had response of IVC thrombus, and 30 (42%) had no or minimal response to SBRT. Actuarial OS in responders and non-responders were 14.4 months (95% CI 9.4-19.2) and 7.4 months (95% CI 4.9-9.7), p-value: 0.022. Six and 12 months survival in responders and non-responders were 65.7% and 37% and 49% and 24.6%, respectively. Post-SBRT, 4 (12%) patients underwent transarterial chemoembolization (TACE) 3 patients (8%) and 1 patient (4%) transarterial radioembolization (TARE). Post-CK, (<4 weeks) 2 patients (4%) had decompensation. CONCLUSIONS: PVT response or recanalization after SBRT is a statistically significant prognostic factor for survival function in HCC-PVT.

A review on radiation induced nausea and vomiting: "Current management strategies and prominence of radio sensitizers".

Radiations dissipated are high energy waves used mostly as treatment intervention in controlling the unwanted multiplication of cell. About 60%-65% of cancer treatment requires radiation therapy and 40%-80% of radiation therapy causes RINV which are true troublemakers. Radiation therapy (RT) is targeted therapy mostly used to treat early stages of tumour and prevent their reoccurrence. They mainly destroy the genetic material (DNA) of cancerous cells to avoid their unwanted growth and division. The RINV affects the management and quality of life of patients which further reduces the patient outcome. RINV depends on RT related factors (dose, fractionation, irradiation volume, RT techniques) and patient related factors like (gender, health conditions, age, concurrent chemotherapy, psychological state, and tumour stage). RT is an active area of research and there is only limited progress in tackling the RINV crisis. Advanced technological methods are adopted that led to better understanding of total lethal doses. Radiation therapy also affects the immunity system that leads to radiation induced immune responses and inflammation. Radio sensitizers are used to sensitize the tumour cells to radiations that further prevent the normal cell damage from radiation exposure. There is a need for future studies and researches to re-evaluate the data available from previous trials in RINV to make better effective antiemetic regimen. The article focuses on radiation therapy induced nausea and vomiting along with their mechanism of action and treatment strategies in order to have a remarkable patient care.

Dosimetric Comparison of Four Different Radiotherapy Planning Techniques for Adjuvant Radiotherapy of Left-Sided Breast, Axilla, and Supraclavicular Fossa.

Purpose/Aim: Forward planned intensity-modulated radiotherapy (forward IMRT) with breath-hold (BH) technique is considered optimal by most practitioners for treating left-sided breast cancer. Regional nodal irradiation including axilla and supraclavicular fossa (SCF) increases can increase dose-to-organs at risk (OAR) especially lung. This study was done to assess the potential of inverse planned IMRT (inverse IMRT) to achieve significant reduction in dose to OAR. Materials and Methods: Ten patients with left-sided breast cancer treated with Active Breath Co-ordinator BH technique were included in the study. Forward IMRT plans were generated in both BH and free breathing (FB) scans. Inverse IMRT plans were generated in FB scan using Tomotherapy-Direct and Tomotherapy-Helical techniques. Contouring was done as per the ESTRO consensus contouring guidelines. The dose prescribed was 40 Gy in 15 fractions. Statistical significance was tested using one-way ANOVA for parametric data and Kruskall-Wallis test for nonparametric data. Multiple comparison tests were done by using Bonferroni test. P <0.05 was considered to denote statistical significance. Results: Inverse IMRT plans achieved superior homogeneity index compared to forward IMRT with BH. Tomotherapy-Direct reduced dose to ipsilateral lung, compared to the forward IMRT with BH while achieving similar doses to other OAR. Tomotherapy-Helical plans achieved significantly better conformity index and reduced maximum dose to left anterior descending artery compared to forward IMRT plans, but low dose to other OAR was significantly worse. Conclusion: For left-sided breast, axilla, and SCF radiotherapy, inverse IMRT with Tomotherapy-Direct plan achieved better homogeneity index and reduced dose to ipsilateral lung compared to forward IMRT with BH.

Prospective evaluation of fiducial marker placement quality and toxicity in liver CyberKnife stereotactic body radiotherapy.

BACKGROUND: Evaluate morbidities and "quality" of fiducial marker placement in primary liver tumours (hepatocellular carcinoma [HCC]) for CyberKnife. MATERIALS AND METHODS: Thirty-six HCC with portal vein thrombosis(PVT) were evaluated for "quality" of fiducial placement, placement time, pain score, complications, recovery time and factors influencing placement. RESULTS: One hundred eight fiducials were placed in 36 patients. Fiducial placement radiation oncologist score was "good" in 24(67%), "fair" in 4(11%), and "poor" in 3(8%) patients. Concordance with radiologist score in "poor", "fair", and "good" score was 2/2(100%), 4/5(80%), and 24/27(89%), respectively(p=0.001). Child-Pugh score(p=0.080), performance status(PS) (p=0.014) and accrued during "learning curve"(p=0.013) affected placement score. Mean placement time(p=0.055), recovery time(p=0.025) was longer and higher major complications(p=0.009) with poor PS. Liver segment involved(p=0.484) and the Barcelona Clinic Liver Cancer(BCLC) stage did not influence placement score. "Good" placement score was 30% in first cohort whereas 93% in last cohort(p=0.023). Time for placement was 42.2 and 14.3 minutes, respectively(p=0.069). Post-fiducial pain score 0-1 in 26 patients(72%) and pain score 3-4 was in 2(6%). Five patients (14%) admitted in "day-care"(2 mild pneumothorax, 3 pain). Mortality in 1 patient(3%) admitted for hemothorax. CONCLUSION: Fiducial placement is safe and in experienced hands, "quality" of placement is "good" in majority. Major complications and admission after fiducial placement are rare. Complications, fiducial placement time, recovery time is more during the "learning curve". Poor Child-Pugh score, extensive liver involvement, poor PS have higher probability of complications.

Effect of Arg399Gln single-nucleotide polymorphism in XRCC1 gene on survival rate of Indian squamous cell head-and-neck cancer patients.

BACKGROUND: Head-and-neck squamous cell carcinoma (HNSCC) is one of the most common cancers that contribute to 20%-40% of all cancer incidences in India. Indian patients with HNSCC are mostly associated with tobacco usage and may have different genetic alterations compared with Western patients who are mostly associated with human papillomavirus infection. Polymorphisms in DNA repair genes are correlated to individuals' susceptibility and progression of cancer. XRCC1 is a DNA repair enzyme. MATERIALS AND METHODS: In the present prospective study, Indian population of HNSCC patients (n = 45) were screened for Arg399Gln variant of XRCC1 using polymerase chain reaction-restriction fragment length polymorphism technique, prospective evaluation of the patients was done after treatment, and the single-nucleotide polymorphism results were correlated to survival functions. RESULTS: Out of 45 patients, 28 patients were Arg/Arg, 12 patients were Arg/Gln, and 5 patients were Gln/Gln. Overall survival for the entire cohort and Arg/Arg, Arg/Gln, and Gln/Gln cohort was 36.3 (95% confidence interval [CI]: 33-39.5), 38.6 (95% CI: 35.3-41.9), 35.8 (95% CI: 28.6-42.9), and 26.4 (95% CI: 13.7-39.1) months (P = 0.097), respectively. Progression-free survival (PFS) of the entire patient cohort and Arg/Arg, Arg/Gln, and Gln/Gln cohort was 35.2 (95% CI: 31.4-39.1), 38.2 (95% CI: 34.3-42.1), 32.7 (95% CI: 26.2-39.1), and 22.3 (95% CI: 9.4-35.3) (P = 0.061), respectively. CONCLUSIONS: This study suggests that HNSCC patients with Gln substitution in place of Arg at position 399 (both homozygous and heterozygous) in XRCC1 protein have significantly inferior survival functions, higher recurrence rate, and events after radical treatment.

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.

Robotic radiosurgery treatment in liver tumors: Early experience from an Indian center.

PURPOSE: The purpose of this study is to report CyberKnife experience in hepatocellular carcinoma (HCC) and liver metastasis (LM). MATERIALS AND METHODS: Fifty liver lesions in 31 consecutive patients with liver lesion [mean age 54.5 years (range 32-81 years), 77% were male patient, GTV <10cc in 5 patients, 11-90cc in 18 & >90cc in 8 patients respectively. Eighty percentage (25/31) had prior treatment (chemotherapy 18 patient & TACE in 7 patients). Dosage schedule was 21-45Gy/3# (mean PTV dose 33Gy, Prescription isodose 84%, target coverage 94%). Mean CI, nCI & HI were 1.19, 1.31 & 1.18 respectively. Mean liver dose was 5.4 Gy, 800 cc liver dose 11.1 Gy. RESULTS: At mean follow-up of 12.5 months (range 1.9-44.6 months), 19 patients were expired and 12 were alive (nine patient with stable disease, two local progression, and one with metastasis). Median overall survival (OS) of all patients are 9 months (1.9-44.6 months), in HCC patients 10.5 months (2.1-44.6 months) and MT 6.5 months (1.9-24.6 months) respectively. Gr-I-II GI toxicities were in 11/50 (22%) patients. OS was influenced by PS (Karnofsky Performance Status 70-80 vs. 90-100: 9.9 vs. 16.4; P = 0.024), Child-Pugh (CP A/B vs. C: 23.6 vs. 6.5; P = 0.069), cirrhosis (only fatty liver vs. diffuse cirrhosis: 17.8 vs. 10.6; P = 0.003), prior treatment (no Rx vs. prior Rx: 30.1 vs. 8.2; P = 0.08), number of lesions (single vs. multiple: 16.4 vs. 6.9; P = 0.001), and target volume (<10 cc vs. >90 cc: 24.6 vs. 11.2; P = 0.03). CONCLUSION: Stereotactic body radiation therapy is a safe and effective treatment. Patient related factors such as performance status, Child-Pugh classification, cirrhosis status, prior treatment, number of liver lesion & target volume (GTV) influence the survival functions.