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Technological advancements in treatment planning and delivery have propelled the use of intensity-modulated radiation therapy (IMRT) in head and neck squamous cell carcinoma (HNSCC). This review compares IMRT with conventional two-dimensional (2D) and/or three-dimensional (3D) radiotherapy (RT) in curative-intent management of HNSCC. Only randomized controlled trials (RCTs) offering curative-intent RT in patients with non-metastatic HNSCC were included. Outcome data was extracted independently by two reviewers, pooled using the Cochrane methodology, and expressed as risk ratio (RR) or hazard ratio (HR) as appropriate with 95% confidence intervals (CIs). Xerostomia was the primary outcome of interest whereas loco-regional control, overall survival and quality-of-life (QOL) were secondary endpoints. Seven RCTs involving 1155 patients directly comparing IMRT with 2D/3D-RT in HNSCC were included. The primary objective in five of seven index RCTs was reduction in xerostomia, with only one trial each using loco-regional control and overall survival as primary endpoints for sample size calculation. The use of IMRT was associated with a 36% relative risk reduction in ≥grade 2 acute xerostomia (RR = 0.64, 95%CI = 0.49-0.84; p = 0.001) compared to 2D/3D-RT. More importantly, IMRT significantly reduced the risk of ≥grade 2 late xerostomia (RR = 0.44, 95%CI = 0.34-0.57; p = 0.00001) compared to non-IMRT techniques at all time-points. Within the limitations of inadequate sample size and low statistical power, IMRT also resulted in 24% relative reduction in the risk of loco-regional relapse (HR = 0.76, 0.57-1.01; p = 0.06) and 30% relative reduction in risk of death (HR = 0.70, 95%CI = 0.57-0.88; p = 0.002) compared to 2D/3D-RT. However, this benefit of IMRT for loco-regional control and overall survival was limited to nasopharyngeal cancer patients alone, with no significant difference in efficacy between the two techniques in patients with cancers of the laryngo-pharynx in this analysis, highlighting the inconsistency in results of subgroup analyses stratified by primary site. Inadequate reporting of data precluded statistically pooling of results for QOL outcomes. There is consistent moderate-quality evidence that IMRT significantly reduces the risk of moderate to severe acute and late xerostomia compared to 2D/3D-RT in curative-intent radiotherapeutic management of HNSCC. However, the quality of evidence regarding the superiority of IMRT over conventional techniques for disease-related endpoints is rather low due to relative lack of power and inconsistency of results precluding robust conclusions.

BackgroundThere exists lack of consensus worldwide regarding the most optimal adjuvant therapy regimen in elderly patients with newly-diagnosed glioblastoma (GBM).PurposeTo identify the most optimal adjuvant therapy regimen in elderly GBM patients through systematic review and network meta-analysis.MethodsProspective trials randomly assigning elderly GBM patients post-operatively to any adjuvant therapy regimen were included. The primary outcome measure was overall survival. Numbers of events, patients at-risk, and censored patients for survival were estimated from Kaplan–Meier survival curves in the interval of 0–12 months. The total person-time at risk and the mortality × 100 person-months was also estimated. The relative ranking probability of each treatment and rankograms were used to estimate the hierarchy of each intervention in terms of overall survival. The mean rank values and the surface under the cumulative ranking (SUCRA) curves were also calculated.ResultsA systematic literature search identified 1278 abstracts, that were screened to retrieve full-text manuscripts of potentially eligible articles. After detailed assessment, data from 1569 patients in 7 randomized controlled trials (RCTs) treated with one of following regimens was extracted and analyzed: normofractionated radiotherapy (RT) delivered over 5.5–6 weeks; moderately hypofractionated RT (2–3 weeks) either alone or in combination with temozolomide or bevacizumab; extremely hypofractionated RT (1-week); temozolomide monotherapy; and best supportive care alone. In terms of overall survival, moderately hypofractionated RT (3-weeks) with concurrent and adjuvant temozolomide emerged as the best and second-best adjuvant therapy option with 81% probability and 99.1% probability respectively. Using SUCRA, the surface area for moderately hypofractionated RT (3-weeks) with concurrent and adjuvant temozolomide reached almost 100%, confirming it as the best intervention. As expected, best supportive care alone was ranked as the worst treatment strategy.ConclusionModerately hypofractionated RT (3-weeks) with concurrent and adjuvant temozolomide is the most optimal and preferred adjuvant therapeutic regimen in elderly GBM.

Purpose Our objective was to conduct a systematic review and meta-analysis of studies assessing the diagnostic performance of 18 F-fluorodeoxyglucose positron emission tomography (FDG PET) with or without computed tomography (CT) in post-treatment response assessment and/or surveillance imaging of head and neck squamous cell carcinoma (HNSCC). Methods A systematic search of the indexed medical literature was done using appropriate keywords to identify relevant studies. Metrics of diagnostic test accuracy, viz. sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were extracted from individual studies and combined using a random effects model to yield weighted mean pooled estimates with 95% confidence intervals (95% CI). The impact of timing of post-treatment scan, study quality and advancements in PET technology was explored through meta-regression. Results A total of 51 studies involving 2,335 patients were included in the meta-analysis. The weighted mean (95% CI) pooled sensitivity, specificity, PPV and NPV of post-treatment FDG PET(CT) for the primary site was 79.9% (73.7–85.2%), 87.5% (85.2–89.5%), 58.6% (52.6–64.5%) and 95.1% (93.5–96.5%), respectively. Similar estimates for the neck were 72.7% (66.6–78.2%), 87.6% (85.7–89.3%), 52.1% (46.6–57.6%) and 94.5% (93.1–95.7%), respectively. Scans done ≥12 weeks after completion of definitive therapy had moderately higher diagnostic accuracy on meta-regression analysis using time as a covariate. Conclusion The overall diagnostic performance of post-treatment FDG PET(CT) for response assessment and surveillance imaging of HNSCC is good, but its PPV is somewhat suboptimal. Its NPV remains exceptionally high and a negative post-treatment scan is highly suggestive of absence of viable disease that can guide therapeutic decision-making. Timing of post-treatment imaging has a significant, though moderate impact on diagnostic accuracy.

Purpose To compare long-term disease-related outcomes and late radiation morbidity between intensity-modulated radiation therapy (IMRT) and three-dimensional conformal radiotherapy (3D-CRT) in head and neck squamous cell carcinoma (HNSCC) in the setting of a prospective randomized controlled trial. Methods Previously untreated patients with early to moderately advanced non-metastatic squamous carcinoma of the oropharynx, larynx, or hypopharynx (T1-T3, N0-N2b, M0) planned for comprehensive irradiation of primary site and bilateral neck nodes were randomly assigned to either IMRT or 3D-CRT after written informed consent. Patients were treated with 6MV photons to a total dose of 70Gy/35 fractions over 7 weeks (3D-CRT) or 66Gy/30 fractions over 6 weeks (IMRT). A sample size of 60 patients was estimated to demonstrate 35% absolute difference in the incidence of ≥grade 2 acute xerostomia between the two arms. All time-to-event outcomes were calculated from date of randomization until the defined event using the Kaplan-Meier method. Results At a median follow-up of 140 months for surviving patients, 10-year Kaplan-Meier estimates of loco-regional control (LRC); progression-free survival (PFS); and overall survival (OS) with 95% confidence interval (95%CI) were 73.6% (95%CI: 61.2–86%); 45.2% (95%CI: 32–58.4%); and 50.3% (95%CI: 37.1–63.5%) respectively. There were no significant differences in 10-year disease-related outcomes between 3D-CRT and IMRT for LRC [79.2% (95%CI: 62.2–96.2%) vs 68.7% (95%CI: 51.1–86.3%), p  = 0.39]; PFS [41.3% (95%CI: 22.3–60.3%) vs 48.6% (95%CI: 30.6–66.6%), p  = 0.59]; or OS [44.9% (95%CI: 25.7–64.1%) vs 55.0% (95%CI: 37–73%), p  = 0.49]. Significantly lesser proportion of patients in the IMRT arm experienced ≥grade 2 late xerostomia and subcutaneous fibrosis at all time-points. However, at longer follow-up, fewer patients remained evaluable for late radiation toxicity reducing statistical power and precision. Conclusions IMRT provides a clinically meaningful and sustained reduction in the incidence of moderate to severe xerostomia and subcutaneous fibrosis compared to 3D-CRT without compromising disease-related outcomes in long-term survivors of non-nasopharyngeal HNSCC.

Advances in diagnostic imaging, pathology, and molecular biology coupled with improvements in neurosurgical approaches, radiotherapeutic techniques, and systemic therapies over the last two decades have vastly improved survival outcomes for medulloblastoma, the most common childhood malignant tumor [...]

Abstract Background: Children on treatment for brain tumor are at high risk of malnutrition and have significant treatment-related toxicities. However, the impact of nutritional status on outcome and toxicity is not well understood. Aim: The objective of this study of children with embryonal brain tumor treated at our center was to understand the impact of nutritional status on treatment-related toxicities. Materials and Methods: We undertook this retrospective audit using a risk-stratified protocol between January 2017 and December 2018. Undernutrition was defined as severe or moderate malnutrition as per the World Health Organization (WHO) criteria. Nutritional status was assessed, and treatment-related toxicity (TRT) and survival rates were analyzed in relation to nutritional status at diagnosis and follow-up. Statistical Analysis Used: IBM SPSS for Windows, Version 24.0. Results: In the cohort of 72 patients with embryonal brain tumors, 64% were undernourished (UN) at the start of chemotherapy, and 2.7% were overweight. At the end of chemotherapy, 61% were UN. During the course of chemotherapy, weight gain was documented in 25% and weight loss in 23.8%. Although chemotherapy toxicity and infection were higher in UN children with medulloblastoma, this was not statistically significant. Both overweight children experienced TRT; one relapsed and subsequently died. Nutritional status did not affect survival rates. Conclusions: Children with embryonal brain tumor are at high nutritional risk, and undernutrition may worsen treatment-related toxicities. Proactive nutritional monitoring and intervention are needed in settings with a high prevalence of malnutrition and infections.

Background: This pilot survey aims to provide an insight into the variations of corticosteroid prescription among health care professionals across the Indian subcontinent and serve as a prerequisite for the future development of corticosteroid therapy guidelines in brain tumor patients. Materials and Methods: Participants of this anonymized online questionnaire-based survey included health care professionals involved in treating brain tumor patients. Unique links were electronically mailed to health care professionals from a database populated from professional associations. Descriptive statistical analysis, Chi-square test, and/or exact test were used for data analysis. Results: Seventy-three percent of the respondents were radiation oncologists followed by neurosurgeons (23%), medical oncologists (2%), and other specialties (2%). Raised intracranial pressure (90%) was the commonest indication for prescribing corticosteroids. Fifty percent of neurosurgeons preferred corticosteroids to be given routinely for all patients undergoing surgery for brain tumors while 64% of the radiation oncologists would prescribe based on imaging findings and/or on appearance of neurologic symptoms. Most of the respondents (90%) used a flat dosage pattern for determining the starting dose of corticosteroids. Emerging data about the long-term use of corticosteroids having a negative impact on the survival of brain tumor patients were not known by 52% of the respondents. The majority of the practitioners (94%) agreed regarding the formulation of evidence-based guidelines for prescribing corticosteroids in brain tumor patients. Conclusion: In view of the wide variations of corticosteroid therapy practices among health care professionals across various parts of the world, our pilot survey provides significant information which can act as a suitable benchmark to form uniform practice guidelines.

Background Diffuse gliomas like glioblastoma, astrocytoma, and oligodendroglioma are defined by complex heterogeneity in imaging and molecular patterns. Traditional diagnosis relies severely on invasive biopsies and human interpretation of MRI scans, which are subjective and severely limited in capturing the complete volumetric and biological heterogeneity of the tumor. Artificial Intelligence (AI) can potentially enhance glioma tumor subtype classification through the analysis and interpretation of medical imaging information. Machine learning, a branch of AI, is key to discovering patterns and characteristics in the data to enable predictive models for prognosis and diagnosis. AI can process MRI scans to derive tumor shape, size, and texture information, and process large datasets to define risk factors and features. This method may improve the speed and accuracy of glioma subtype diagnoses and facilitate individualized treatment planning. Aim In the current study, we have evaluated the performance of multiple machine learning classifiers in distinguishing between glioblastoma, astrocytoma, and oligodendroglioma based on radiomics and clinical features. The goal of the study was to identify effective feature selection techniques that enhance the accuracy and reliability of classification models and to develop a methodology that can be adapted for use with imaging data collected at our institute, supporting future diagnostic workflows. Methods A total 729 radiomic features were expended from TCIA for the experimental analysis. The radiomic signature of significant features has been created for every sample using XGBoost decision tree, XGBoost random forest, CatBoost and Light GBM tree based feature selection algorithm. The experimentation has been done by training 13 different models. The hyper parameters of each of the model has been tuned and different performance parameters like accuracy, precision, recall, F1 score and AUC-ROC curve have been compared. Results Feature selection using XGBoost decision tree, XGBoost random forest, Catboost and Light GBM tree- based classifier is used for selecting the top 21, 37, 71 and 82 features based on feature importance score. The experimental results shows that the feature subset by XGBoost decision tree method gave the best performance as compared to others. A total of 13 classification models were trained and tested giving a best tenfold validation accuracy, test accuracy, macro F1-score of 95.2%, 77%, 0.716 and AUC of 0.92 for Catboost classifier.

Introduction Craniospinal irradiation (CSI) forms an integral role in the management of primary brain tumors like embryonal tumors (medulloblastoma), non-seminomatous germ cell tumors, metastatic ependymoma, etc. The cranial component with radiation of whole brain and boost can lead to decline in neurocognitive function. Memantine is an NMDA receptor antagonist with an established role in reducing radiation-induced neurocognitive decline in patients treated with whole brain radiotherapy, but the benefit in pediatric and adults treated with CSI remains unclear. Methods This is a phase 3 open-label, randomized controlled trial. Pediatric and young adults (5 to 39 years) treated with CSI will be eligible for the study. Patients will be randomized in 1: 1 accounting for stratification factors such as age, CSI dose, location of tumor boost, and use of chemotherapy. Patients in the experimental arm will receive memantine 5 mg once daily for 1 week, 5 mg twice daily for 1 week, and finally escalated to 10 mg twice daily for 6 months. The primary endpoint will be cognitive deterioration-free survival (CDFS) at 2 years, with secondary endpoints being safety and compliance of memantine, slope of decline of neurocognitive scores, and survival. To demonstrate the improvement of 2-year CDFS of 75% in memantine arm compared to 50% in standard arm, 84 patients need to be evaluated (alpha 0.05 and power 80%). Considering an attrition of 20%, a total of 101 patients will be randomized. Discussion If trial results are positive memantine will be established as a new standard of care to be used with CSI. Trial registration The trial is registered on ClinicalTrials.gov (study identifier NCT06275035) and Clinical Trial Registry India (CTRI/2024/02/062273).

Purpose Nearly 10% of patients with adult diffuse glioma develop clinically significant myelotoxicity while on temozolomide (TMZ) leading to treatment interruptions. This study aimed to assess single nucleotide polymorphisms (SNPs) in the O 6 -methylguanine-DNA methyltransferase ( MGMT ) gene in adults with biopsy-proven diffuse glioma who develop TMZ-induced myelotoxicity and correlate their presence with severity and duration of such toxicity. Methods This study assessed 33 adults treated with TMZ for diffuse glioma who developed ≥ grade 2 thrombocytopenia and/or ≥ grade 3 neutropenia. Genomic DNA was extracted from peripheral blood cells for MGMT SNP analysis after written informed consent. TMZ-induced severe myelotoxicity (≥ grade 3) was correlated with three specified SNPs commonly seen in the MGMT gene (L84F, I143V/K178R) using chi-square test or Fischer’s exact test as appropriate. Results Of the 33 adults, 24 (72.7%) experienced ≥ grade 3 thrombocytopenia and/or neutropenia, while 9 (27.3%) developed grade 2 thrombocytopenia only. The variant T allele of L84F was expressed in 28.7% (19/66) of analyzed alleles, which was substantially higher than previously reported for South Asian ancestry. The variant G allele of I143V/K178R was expressed in 9.3% (6/64) of analyzed alleles. Of which 3 patients showed statistically significant association with prolonged myelosuppression for > 2 months (p = 0.03). No significant correlation was established between the mentioned SNPs and severe myelotoxicity. Conclusions There is substantially higher frequency of variant T allele (L84F) in Indian patients than previously reported for South Asians. The presence of specific SNPs in the MGMT gene correlates with prolonged duration but not severity of TMZ-induced myelotoxicity.