A systematic review and meta-analysis informing the role of adjuvant radiotherapy (RT) in Grade 2 and 3 oligodendroglioma.

BACKGROUND AND PURPOSE: Evidence and clinical guidelines support the use of adjuvant RT in high-risk low-grade gliomas. However, patients with oligodendroglioma have a more indolent disease course and delaying or avoiding RT is often considered to reduce treatment-related toxicities. As the optimal adjuvant management for oligodendroglioma is unclear, we aimed to assess the effect of adjuvant RT on overall survival (OS) and progression-free survival (PFS). METHODS: MEDLINE, EMBASE, CENTRAL and CINAHL were searched from January 1990 to February 2023 for studies comparing adjuvant RT versus no adjuvant RT for patients with oligodendroglioma. RESULTS: This review found 17 eligible studies including 14 comparative retrospective studies and 3 randomized controlled trials. Using random-effects model, the results suggested that adjuvant RT improved OS by 28 % (HR 0.72, 95 % CI (0.56-0.93), I2 = 86 %), and PFS by 48 % (HR 0.52, (95 % CI 0.40-0.66), I2 = 48 %) compared to patients without adjuvant RT. Subgroup analysis showed that upfront adjuvant RT improved OS and PFS compared to salvage RT. There were no significant differences in OS and PFS between adjuvant RT versus adjuvant chemotherapy. There was improvement in PFS but not OS for adjuvant chemoradiotherapy versus adjuvant chemotherapy alone. Adjuvant RT improved OS in WHO Grade 3 but not WHO Grade 2 oligodendroglioma. CONCLUSION: Overall, adjuvant RT improved OS and PFS in patients with oligodendroglioma. In patients with low-risk features (e.g. Grade 2, gross total resection), alternative approaches and individualization of management such as adjuvant chemotherapy alone may be reasonable considering the lack of survival benefit. Future efforts should prospectively investigate these treatment regimens on molecularly-classified oligodendroglioma patients (defined by presence of IDH mutation and 1p/19q co-deletion), balancing between maximizing survival outcomes and reducing RT-related toxicities.

Evaluation of ex vivo drug combination optimization platform in recurrent high grade astrocytic glioma: An interventional, non-randomized, open-label trial protocol.

INTRODUCTION: High grade astrocytic glioma (HGG) is a lethal solid malignancy with high recurrence rates and limited survival. While several cytotoxic agents have demonstrated efficacy against HGG, drug sensitivity testing platforms to aid in therapy selection are lacking. Patient-derived organoids (PDOs) have been shown to faithfully preserve the biological characteristics of several cancer types including HGG, and coupled with the experimental-analytical hybrid platform Quadratic Phenotypic Optimization Platform (QPOP) which evaluates therapeutic sensitivity at a patient-specific level, may aid as a tool for personalized medical decisions to improve treatment outcomes for HGG patients. METHODS: This is an interventional, non-randomized, open-label study, which aims to enroll 10 patients who will receive QPOP-guided chemotherapy at the time of first HGG recurrence following progression on standard first-line therapy. At the initial presentation of HGG, tumor will be harvested for primary PDO generation during the first biopsy/surgery. At the point of tumor recurrence, patients will be enrolled onto the main study to receive systemic therapy as second-line treatment. Subjects who undergo surgery at the time of recurrence will have a second harvest of tissue for PDO generation. Established PDOs will be subject to QPOP analyses to determine their therapeutic sensitivities to specific panels of drugs. A QPOP-guided treatment selection algorithm will then be used to select the most appropriate drug combination. The primary endpoint of the study is six-month progression-free survival. The secondary endpoints include twelve-month overall survival, RANO criteria and toxicities. In our radiological biomarker sub-study, we plan to evaluate novel radiopharmaceutical-based neuroimaging in determining blood-brain barrier permeability and to assess in vivo drug effects on tumor vasculature over time. TRIAL REGISTRATION: This trial was registered on 8th September 2022 with ClinicalTrials.gov Identifier: NCT05532397.

Is Gamma Knife surgery, omitting adjunct whole brain radiation treatment, feasible for patients with 20 or more brain metastases?

Background: The importance of the number of brain metastases (BM) when deciding between whole brain radiation treatment (WBRT) and radiosurgery is controversial. We hypothesized that the number of BM is of limited importance when deciding radiation strategy, and offered Gamma Knife surgery (GKS) also for selected patients with 20 or more BM. Methods: The outcome following single session GKS for 75 consecutive patients harboring 20 or more (20+) BM was analyzed. Data was collected both retro- and prospectively. Results: The median survival time was 9 months. Two grade 3 complications occurred, 1 resolved and 1 did not. Sex and clinical condition at the time of GKS (ECOG value) were the only parameters significantly related to survival time. Eighteen patients developed leptomeningeal dissemination with or without distant recurrences (DR), and another 32 patients developed DR a total of 73 times. DR was managed with GKS 24 times, with WBRT 3 times and with systemic treatment or best supportive care 46 times. The median time to developing DR was unrelated to the number of BM, but significantly longer for patients older than 65 years, as well as for patients with NSCLC. Conclusions: GKS is a reasonable treatment option for selected patients with 20 or more BM. It is better to decide the optimal management of post-GKS intracranial disease progression once it occurs rather than trying to prevent it by using adjunct WBRT.

Adjuvant radiotherapy versus observation after gross total resection of WHO grade II ependymoma: a systematic review and individual-participant data meta-analysis.

BACKGROUND: The role of adjuvant radiotherapy (RT) after gross total resection (GTR) of the World Health Organization (WHO) grade II ependymoma is controversial. Therefore, we aimed to compare the outcomes of adjuvant RT against observation after GTR of WHO grade II ependymoma. We also compared the outcomes of adjuvant RT against observation after subtotal resection (STR) of WHO grade II ependymoma and performed further subgroup analysis by age and tumor location. METHODS: PubMed and Embase were systematically reviewed for studies published up till 25 November 2022. Studies that reported individual-participant data on patients who underwent surgery followed by adjuvant RT/observation for WHO grade II ependymoma were included. The exposure was whether adjuvant RT was administered, and the outcomes were recurrence and overall survival (OS). Subgroup analyses were performed by the extent of resection (GTR or STR), tumor location (supratentorial or infratentorial), and age at the first surgery (<18 or ≥18 years old). RESULTS: Of the 4,647 studies screened, three studies reporting a total of 37 patients were included in the analysis. Of these 37 patients, 67.6% (25 patients) underwent GTR, and 51.4% (19 patients) underwent adjuvant RT. Adjuvant RT after GTR was not significantly associated with both recurrence (odds ratio =5.50; 95% confidence interval: 0.64-60.80; P=0.12) and OS (P=0.16). Adjuvant RT was also not significantly associated with both recurrence and OS when the cohort was analyzed as a whole and on subgroup analysis by age and tumor location. However, adjuvant RT was associated with significantly longer OS after STR (P=0.03) with the median OS being 6.33 years, as compared to 0.40 years for patients who underwent STR followed by observation. CONCLUSIONS: Based on our meta-analysis of 37 patients, administration of adjuvant RT after GTR was not significantly associated with improvement in OS or recurrence in patients with WHO grade II ependymoma. However, due to the small number of patients included in the analysis, further prospective controlled studies are warranted.

Radiation therapy with phenotypic medicine: towards N-of-1 personalization.

In current clinical practice, radiotherapy (RT) is prescribed as a pre-determined total dose divided over daily doses (fractions) given over several weeks. The treatment response is typically assessed months after the end of RT. However, the conventional one-dose-fits-all strategy may not achieve the desired outcome, owing to patient and tumor heterogeneity. Therefore, a treatment strategy that allows for RT dose personalization based on each individual response is preferred. Multiple strategies have been adopted to address this challenge. As an alternative to current known strategies, artificial intelligence (AI)-derived mechanism-independent small data phenotypic medicine (PM) platforms may be utilized for N-of-1 RT personalization. Unlike existing big data approaches, PM does not engage in model refining, training, and validation, and guides treatment by utilizing prospectively collected patient's own small datasets. With PM, clinicians may guide patients' RT dose recommendations using their responses in real-time and potentially avoid over-treatment in good responders and under-treatment in poor responders. In this paper, we discuss the potential of engaging PM to guide clinicians on upfront dose selections and ongoing adaptations during RT, as well as considerations and limitations for implementation. For practicing oncologists, clinical trialists, and researchers, PM can either be implemented as a standalone strategy or in complement with other existing RT personalizations. In addition, PM can either be used for monotherapeutic RT personalization, or in combination with other therapeutics (e.g. chemotherapy, targeted therapy). The potential of N-of-1 RT personalization with drugs will also be presented.

Is two-staged gamma knife surgery a reasonable management option for very large cerebellar metastases? A case series of three patients.

OBJECTIVE: Two-staged gamma knife surgery (GKS) is a method that may extend the upper tumor volume limit for using GKS in the management of brain metastases. However, the safety of treating very large posterior fossa lesions with this technique has not been well demonstrated. Therefore, we analyzed our experience in treating cerebellar metastases larger than 12 cm3 with two-staged GKS. METHODS: Four consecutive patients harboring 12 to 30 cm3 cerebellar metastases scheduled two-staged GKS were included in the study, and all but one patient completed the treatment. The treatment doses were 10-13 Gy. All patients were followed with regular MR imaging and clinical assessments, and the tumor volumes were measured on all treatment and follow-up images. RESULTS: Tumor progression was not demonstrated in any of the patients. Tumor volumes decreased by, on average, more than half between the two stages. The median survival was 22 months, and no patient died due to intracranial tumor progression. Peritumoral edema at the first GKS resolved in all patients, replaced by asymptomatic mild T2 changes in two of them not requiring any treatment. No radiation-induced complication has developed thus far. CONCLUSION: Staged GKS seems to be a feasible management option for very large cerebellar metastases.

Management of first recurrence or progression of craniopharyngioma after resection alone: A systematic review and individual-participant data meta-analysis.

The initial management of craniopharyngioma is generally either gross total resection (GTR) or subtotal resection (STR) with adjuvant radiotherapy (RT). However, the optimal management strategy for recurrent/progressive craniopharyngioma remains unclear. In this systematic review and individual participant data meta-analysis, we aimed to compare the outcomes of surgery and/or RT for the first recurrence/progression of craniopharyngioma after resection alone. The exposure was the treatment that was administered for the first recurrence/progression, and the outcomes were tumor regrowth and overall survival (OS). Subgroup analyses were performed by age at the treatment for the first recurrence/progression (<18 or ≥ 18 years old), duration between the first treatment and the first recurrence/progression (<2 or ≥ 2 years), and the initial treatment that was administered (STR or GTR). Of the 2932 studies screened, 11 studies reporting a total of 80 patients were included. Across almost all subgroups, patients who received RT for the first recurrence/progression had a significantly lower risk of tumor regrowth than those who did not, regardless of whether surgery was performed and the extent of resection. There was no significant association between the treatment administered for the first recurrence/progression and OS, except for patients with a recurrence/progression < 2 years after the first treatment, where GTR was associated with a higher risk of mortality. For patients with the first recurrence/progression of craniopharyngioma after resection alone, RT should be considered for better local control. In cases where RT is not administered, GTR is preferred over STR provided it can be safely performed, for improved local control.

Intracranial Germ Cell Tumors.

Intracranial germ cell tumors are rare tumors occurring in adolescents and young adults, which include germinomas and non-germinomatous type germ cell tumors (NGGCT). In the past few decades, cooperative trial groups in Europe and North America have developed successful strategies to improve survival outcomes and decrease treatment-related toxicities. New approaches to establishing diagnosis have deferred the need for radical surgery. The 5-year event-free survival (EFS) is above 90% and even patients who present with metastatic germinoma can still be cured with chemotherapy and craniospinal irradiation. The combination of surgery, chemotherapy, and radiation therapy is tailored to patients based on grouping and staging. For NGGCT, neoadjuvant chemotherapy followed by delayed surgery for residual disease and radiotherapy can yield a 5-year EFS of 70%. Further strategies should focus on reducing long-term complications while preserving high cure rates.

CURATE.AI COR-Tx platform as a digital therapy and digital diagnostic for cognitive function in patients with brain tumour postradiotherapy treatment: protocol for a prospective mixed-methods feasibility clinical trial.

INTRODUCTION: Conventional interventional modalities for preserving or improving cognitive function in patients with brain tumour undergoing radiotherapy usually involve pharmacological and/or cognitive rehabilitation therapy administered at fixed doses or intensities, often resulting in suboptimal or no response, due to the dynamically evolving patient state over the course of disease. The personalisation of interventions may result in more effective results for this population. We have developed the CURATE.AI COR-Tx platform, which combines a previously validated, artificial intelligence-derived personalised dosing technology with digital cognitive training. METHODS AND ANALYSIS: This is a prospective, single-centre, single-arm, mixed-methods feasibility clinical trial with the primary objective of testing the feasibility of the CURATE.AI COR-Tx platform intervention as both a digital intervention and digital diagnostic for cognitive function. Fifteen patient participants diagnosed with a brain tumour requiring radiotherapy will be recruited. Participants will undergo a remote, home-based 10-week personalised digital intervention using the CURATE.AI COR-Tx platform three times a week. Cognitive function will be assessed via a combined non-digital cognitive evaluation and a digital diagnostic session at five time points: preradiotherapy, preintervention and postintervention and 16-weeks and 32-weeks postintervention. Feasibility outcomes relating to acceptability, demand, implementation, practicality and limited efficacy testing as well as usability and user experience will be assessed at the end of the intervention through semistructured patient interviews and a study team focus group discussion at study completion. All outcomes will be analysed quantitatively and qualitatively. ETHICS AND DISSEMINATION: This study has been approved by the National Healthcare Group (NHG) DSRB (DSRB2020/00249). We will report our findings at scientific conferences and/or in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04848935.

Emergent radiotherapy for spinal cord compression/impingement-a narrative review.

BACKGROUND AND OBJECTIVE: Malignant epidural spinal cord compression (MESCC), often presenting with back pain and motor/sensory deficits, is associated with poor survival, particularly when there is loss of ambulation. The purpose of this review is to evaluate the literature and discuss appropriate workup and management of MESCC, specifically in the emergent setting. METHODS: A PubMed search was conducted on "spinal cord compression" and "radiation therapy." Articles were analyzed for the purpose of this narrative review. KEY CONTENT AND FINDINGS: If MESCC is suspected, neurologic examination and complete spine imaging are recommended. Emergent treatment is indicated if there is radiographic evidence of high-grade compression and/or clinically significant motor deficits. Treatment involves a combination of medical management, surgical decompression, radiation therapy (RT), and rehabilitation. For motor deficits, emergent initiation of high dose steroids is recommended. Circumferential surgical decompression ± stabilization followed by RT provides superior clinical outcomes than RT alone. For patients whom surgery is not reasonable, RT alone may provide significant treatment response which depends on radioresponsiveness of the pathology. Systemic therapy, if indicated, is typically reserved till after primary treatment of MESCC, but patients with chemoresponsive tumors may receive primary chemotherapy. The selected RT schedule should be personalized to each patient and commonly is 30 Gy in 10 fractions (fx), 20 Gy in 5 fx, or 8 Gy in 1 fx. MESCC recurrence may be treated with additional RT, if within the spinal cord tolerance, or surgery. Stereotactic body radiation therapy (SBRT) has been used for high grade MESCC in patients with relatively intact neurologic function at a few centers with a very robust infrastructure to support rapid initiation of treatment within a short period of time, but is generally not feasible for most clinical practices. SBRT may be advantageous for low grade MESCC, recurrence, or in the post-operative setting. Detection of MESCC prior to development of high-grade compression or deterioration of neurologic function may allow patients to benefit more from advanced therapies and improve prognosis. CONCLUSIONS: MESCC is a devastating condition; optimal treatment should be personalized to each patient and approached collaboratively by a multidisciplinary team.

Presenting characteristics, histological subtypes and outcomes of adult central nervous system tumours: retrospective review of a surgical cohort.

Introduction: The most recent local study on the incidence of histological subtypes of all brain and spinal tumours treated surgically was published in 2000. In view of the outdated data, we investigated the presenting characteristics, histological subtypes and outcomes of adult patients who underwent surgery for brain or spinal tumours at our institution. Methods: A single-centre retrospective review of 501 patients who underwent surgery for brain or spinal tumours from 2016 to 2020 was conducted. The inclusion criteria were (a) patients who had a brain or spinal tumour that was histologically verified and (b) patients who were aged 18 years and above at the time of surgery. Results: Four hundred and thirty-five patients (86.8%) had brain tumours and 66 patients (13.2%) had spinal tumours. Patients with brain tumours frequently presented with cranial nerve palsy, headache and weakness, while patients with spinal tumours frequently presented with weakness, numbness and back pain. Overall, the most common histological types of brain and spinal tumours were metastases, meningiomas and tumours of the sellar region. The most common complications after surgery were cerebrospinal fluid leak, diabetes insipidus and urinary tract infection. In addition, 15.2% of the brain tumours and 13.6% of the spinal tumours recurred, while 25.7% of patients with brain tumours and 18.2% of patients with spinal tumours died. High-grade gliomas and metastases had the poorest survival and highest recurrence rates. Conclusion: This study serves as a comprehensive update of the epidemiology of brain and spinal tumours and could help guide further studies on brain and spinal tumours.

Emergent radiotherapy for brain and leptomeningeal metastases: a narrative review.

BACKGROUND AND OBJECTIVE: As novel systemic therapies allow patients to live longer with cancer, the risk of developing central nervous system (CNS) metastases increases and providers will more frequently encounter emergent presentation of brain metastases (BM) and leptomeningeal metastases (LM). Management of these metastases requires appropriate work-up and well-coordinated multidisciplinary care. We set out to perform a review of emergent radiotherapy (RT) for CNS metastases, specifically focusing on BM and LM. METHODS: We review the appropriate pathways for workup and initial management of BM and LM, while reviewing the literature supporting emergent treatment of these entities with surgery, systemic anti-cancer therapy, and RT. To inform this narrative review, literature searches in PubMed and Google Scholar were conducted, with preference given to articles employing modern RT techniques, when applicable. Due to the paucity of high-quality evidence for management of BM and LM in the emergent setting, discussion was supplemented by the authors' expert commentary. KEY CONTENT AND FINDINGS: This work highlights the importance of surgical evaluation, particularly for patients presenting with significant mass effect, hemorrhagic metastases, or increased intracranial pressure. We review the rare situations where emergent initiation of systemic anti-cancer therapy is indicated. When defining the role of RT, we review factors guiding selection of appropriate modality, treatment volume, and dose-fractionation. Generally, 2D- or 3D-conformal treatment techniques prescribed as 30 Gy in 10 fractions or 20 Gy in 5 fractions, should be employed in the emergent setting. CONCLUSIONS: Patients with BM and LM present from a diverse array of clinical situations, requiring well-coordinated multidisciplinary management, and there is a paucity of high-quality evidence guiding such management decisions. This narrative review aims to more thoroughly prepare providers for the challenging situation of emergent management of BM and LM.

Novel 3D printable PEEK-HA-Mg2SiO4 composite material for spine implants: biocompatibility and imaging compatibility assessments.

PURPOSE: To develop a novel 3D printable polyether ether ketone (PEEK)-hydroxyapatite (HA)-magnesium orthosilicate (Mg2SiO4) composite material with enhanced properties for potential use in tumour, osteoporosis and other spinal conditions. We aim to evaluate biocompatibility and imaging compatibility of the material. METHODS: Materials were prepared in three different compositions, namely composite A: 75 weight % PEEK, 20 weight % HA, 5 weight % Mg2SiO4; composite B: 70 weight% PEEK, 25 weight % HA, 5 weight % Mg2SiO4; and composite C: 65 weight % PEEK, 30 weight % HA, 5 weight % Mg2SiO4. The materials were processed to obtain 3D printable filament. Biomechanical properties were analysed as per ASTM standards and biocompatibility of the novel material was evaluated using indirect and direct cell cytotoxicity tests. Cell viability of the novel material was compared to PEEK and PEEK-HA materials. The novel material was used to 3D print a standard spine cage. Furthermore, the CT and MR imaging compatibility of the novel material cage vs PEEK and PEEK-HA cages were evaluated using a phantom setup. RESULTS: Composite A resulted in optimal material processing to obtain a 3D printable filament, while composite B and C resulted in non-optimal processing. Composite A enhanced cell viability up to ~ 20% compared to PEEK and PEEK-HA materials. Composite A cage generated minimal/no artefacts on CT and MR imaging and the images were comparable to that of PEEK and PEEK-HA cages. CONCLUSION: Composite A demonstrated superior bioactivity vs PEEK and PEEK-HA materials and comparable imaging compatibility vs PEEK and PEEK-HA. Therefore, our material displays an excellent potential to manufacture spine implants with enhanced mechanical and bioactive property.

Deep learning assessment compared to radiologist reporting for metastatic spinal cord compression on CT.

Introduction: Metastatic spinal cord compression (MSCC) is a disastrous complication of advanced malignancy. A deep learning (DL) algorithm for MSCC classification on CT could expedite timely diagnosis. In this study, we externally test a DL algorithm for MSCC classification on CT and compare with radiologist assessment. Methods: Retrospective collection of CT and corresponding MRI from patients with suspected MSCC was conducted from September 2007 to September 2020. Exclusion criteria were scans with instrumentation, no intravenous contrast, motion artefacts and non-thoracic coverage. Internal CT dataset split was 84% for training/validation and 16% for testing. An external test set was also utilised. Internal training/validation sets were labelled by radiologists with spine imaging specialization (6 and 11-years post-board certification) and were used to further develop a DL algorithm for MSCC classification. The spine imaging specialist (11-years expertise) labelled the test sets (reference standard). For evaluation of DL algorithm performance, internal and external test data were independently reviewed by four radiologists: two spine specialists (Rad1 and Rad2, 7 and 5-years post-board certification, respectively) and two oncological imaging specialists (Rad3 and Rad4, 3 and 5-years post-board certification, respectively). DL model performance was also compared against the CT report issued by the radiologist in a real clinical setting. Inter-rater agreement (Gwet's kappa) and sensitivity/specificity/AUCs were calculated. Results: Overall, 420 CT scans were evaluated (225 patients, mean age=60 ± 11.9[SD]); 354(84%) CTs for training/validation and 66(16%) CTs for internal testing. The DL algorithm showed high inter-rater agreement for three-class MSCC grading with kappas of 0.872 (p<0.001) and 0.844 (p<0.001) on internal and external testing, respectively. On internal testing DL algorithm inter-rater agreement (κ=0.872) was superior to Rad 2 (κ=0.795) and Rad 3 (κ=0.724) (both p<0.001). DL algorithm kappa of 0.844 on external testing was superior to Rad 3 (κ=0.721) (p<0.001). CT report classification of high-grade MSCC disease was poor with only slight inter-rater agreement (κ=0.027) and low sensitivity (44.0), relative to the DL algorithm with almost-perfect inter-rater agreement (κ=0.813) and high sensitivity (94.0) (p<0.001). Conclusion: Deep learning algorithm for metastatic spinal cord compression on CT showed superior performance to the CT report issued by experienced radiologists and could aid earlier diagnosis.

A deep learning-based technique for the diagnosis of epidural spinal cord compression on thoracolumbar CT.

PURPOSE: To develop a deep learning (DL) model for epidural spinal cord compression (ESCC) on CT, which will aid earlier ESCC diagnosis for less experienced clinicians. METHODS: We retrospectively collected CT and MRI data from adult patients with suspected ESCC at a tertiary referral institute from 2007 till 2020. A total of 183 patients were used for training/validation of the DL model. A separate test set of 40 patients was used for DL model evaluation and comprised 60 staging CT and matched MRI scans performed with an interval of up to 2 months. DL model performance was compared to eight readers: one musculoskeletal radiologist, two body radiologists, one spine surgeon, and four trainee spine surgeons. Diagnostic performance was evaluated using inter-rater agreement, sensitivity, specificity and AUC. RESULTS: Overall, 3115 axial CT slices were assessed. The DL model showed high kappa of 0.872 for normal, low and high-grade ESCC (trichotomous), which was superior compared to a body radiologist (R4, κ = 0.667) and all four trainee spine surgeons (κ range = 0.625-0.838)(all p < 0.001). In addition, for dichotomous normal versus any grade of ESCC detection, the DL model showed high kappa (κ = 0.879), sensitivity (91.82), specificity (92.01) and AUC (0.919), with the latter AUC superior to all readers (AUC range = 0.732-0.859, all p < 0.001). CONCLUSION: A deep learning model for the objective assessment of ESCC on CT had comparable or superior performance to radiologists and spine surgeons. Earlier diagnosis of ESCC on CT could reduce treatment delays, which are associated with poor outcomes, increased costs, and reduced survival.

Design and 3D printing of novel titanium spine rods with lower flexural modulus and stiffness profile with optimised imaging compatibility.

PURPOSE: To manufacture and test 3D printed novel design titanium spine rods with lower flexural modulus and stiffness compared to standard solid titanium rods for use in metastatic spine tumour surgery (MSTS) and osteoporosis. METHODS: Novel design titanium spine rods were designed and 3D printed. Three-point bending test was performed to assess mechanical performance of rods, while a French bender was used to assess intraoperative rod contourability. Furthermore, 3D printed spine rods were tested for CT & MR imaging compatibility using phantom setup. RESULTS: Different spine rod designs generated includes shell, voronoi, gyroid, diamond, weaire-phelan, kelvin, and star. Tests showed 3D printed rods had lower flexural modulus with reduction ranging from 2 to 25% versus standard rod. Shell rods exhibited highest reduction in flexural modulus of 25% (~ 77.4 GPa) and star rod exhibited lowest reduction in flexural modulus of 2% (100.8GPa). 3D printed rod showed reduction in stiffness ranging from 40 to 59%. Shell rod displayed highest reduction in stiffness of 59% (179.9 N/mm) and gyroid had least reduction in stiffness of 40% (~ 259.2 N/mm). Rod bending test showed that except gyroid, other rod designs demonstrated lesser bending difficulty versus standard rod. All 3D printed rods demonstrated improved CT/MR imaging compatibility with reduced artefacts versus standard rod. CONCLUSION: By utilising novel design approach, we successfully generated a spine rod design portfolio with lower flexural modulus/stiffness profile and better CT/MR imaging compatibility for potential use in MSTS/other conditions such as osteoporosis. Thus, exploration of new rod designs in surgical application could enhance treatment outcome and improve quality of life for patients.

Application of Machine Learning for Differentiating Bone Malignancy on Imaging: A Systematic Review.

An accurate diagnosis of bone tumours on imaging is crucial for appropriate and successful treatment. The advent of Artificial intelligence (AI) and machine learning methods to characterize and assess bone tumours on various imaging modalities may assist in the diagnostic workflow. The purpose of this review article is to summarise the most recent evidence for AI techniques using imaging for differentiating benign from malignant lesions, the characterization of various malignant bone lesions, and their potential clinical application. A systematic search through electronic databases (PubMed, MEDLINE, Web of Science, and clinicaltrials.gov) was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A total of 34 articles were retrieved from the databases and the key findings were compiled and summarised. A total of 34 articles reported the use of AI techniques to distinguish between benign vs. malignant bone lesions, of which 12 (35.3%) focused on radiographs, 12 (35.3%) on MRI, 5 (14.7%) on CT and 5 (14.7%) on PET/CT. The overall reported accuracy, sensitivity, and specificity of AI in distinguishing between benign vs. malignant bone lesions ranges from 0.44-0.99, 0.63-1.00, and 0.73-0.96, respectively, with AUCs of 0.73-0.96. In conclusion, the use of AI to discriminate bone lesions on imaging has achieved a relatively good performance in various imaging modalities, with high sensitivity, specificity, and accuracy for distinguishing between benign vs. malignant lesions in several cohort studies. However, further research is necessary to test the clinical performance of these algorithms before they can be facilitated and integrated into routine clinical practice.

Dosimetric comparison between Intensity Modulated Radiation Therapy (IMRT) vs dual arc Volumetric Arc Therapy (VMAT) for nasopharyngeal cancer (NPC): Systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Previous non-randomised studies comparing dosimetric outcomes between advanced techniques such as IMRT and VMAT reported conflicting findings. We thus sought to perform a systematic review and meta-analysis to consolidate the findings of these studies. MATERIALS AND METHODS: We searched PUBMED and EMBASE for eligible studies from their time of inception to 10 March 2022. A random effects model was used to estimate the pooled mean differences (MDs) and their 95% confidence intervals(CIs) for target volume coverage, organ-at-risk(OAR) doses, monitor units(MUs) and treatment delivery times. We also performed a subgroup analysis to evaluate if different treatment planning systems (TPS) (Eclipse, Monaco and Pinnacle) used affected the pooled mean differences. RESULTS: A total of 17 studies (383 patients) were eligible to be included. The pooled results showed that dual arc VMAT reduced D2% of PTV (MD=0.71Gy,95%CI=0.14-1.27,P=0.01), mean left cochlea dose (MD=2.6Gy,95%CI=0.03-5.16,P=0.05), mean right cochlea dose (MD=3.4Gy,95%CI=0.7-6.1,P=0.01), MUs (MD=554.9,95%CI=245.8-863.9,P=0.0004), treatment delivery times (MD=6.7mins,95%CI=4.5-8.9,P<0.0001) and integral dose (MD=0.97Gy,95%CI=0.28-1.67,P=0.006). None of the other indices were significantly better for the IMRT plans. The subgroup analysis showed that the integral dose was significantly lower only for Eclipse (MD=0.88Gy, 95%CI=0.14-1.63, P=0.02). The total MUs was significantly lower only for Eclipse (MD=1035.2, 95%CI=624.6-1445.9, P<0.0001) and Pinnacle (MD=293, 95%CI=15.6-570.5, P=0.04). Similarly, delivery time was also significantly lower only for Eclipse (MD=6.1mins, 95%CI=5.7-6.5, P<0.0001) and Pinnacle (MD=4.9mins, 95%CI=2.6-7.2, P<0.0001). The subgroup analysis however showed that target coverage was superior for the IMRT plans for both Pinnacle (MD=0.48Gy, 95%CI=0.31-0.66, P<0.0001) and Monaco (MD=0.12Gy, 95%CI=0.07-0.17, P<0.0001). CONCLUSION: Dual-arc VMAT plans improved OAR doses, MUs and treatment times as compared to IMRT plans. The different TPS used may modify dosimetric outcomes.

Outcomes of Patients With Spinal Metastases From Prostate Cancer Treated With Conventionally-Fractionated External Beam Radiation Therapy.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To evaluate the outcomes of conventionally-fractionated external beam radiation therapy (cEBRT) in the treatment of prostate cancer spinal metastases (PCSM). METHODS: Patients who received palliative cEBRT for PCSM in our institution between 2008 and 2018 were included. Our outcomes were local progression-free survival (LPFS), overall survival (OS), pain response and toxicities graded using CTCAE version 4.03. Univariable and multivariable Cox proportional hazard regressions were performed to identify predictors for LPFS and OS. RESULTS: A total of 100 patients with 132 sites of PCSM were identified, with a median follow-up of 54 months. Fourteen-percent of patients underwent surgical intervention before receiving cEBRT. Eighteen spinal segments (13.6%) had local progression, with a median time to local progression of 8 months. The median LPFS and OS were 7.8 and 9.0 months, respectively. The complete and partial pain response rates were 57% and 39% respectively. The incidence of grade ≥3 acute toxicities was 11%. Better ECOG performance status (0 to 1), castration-sensitive disease, spinal surgery and use of novel antiandrogen agent were identified as significant predictors for improved OS on multivariable analysis. CONCLUSIONS: In our prostate cancer cohort, cEBRT is an effective treatment modality for local palliation of spinal metastases. More aggressive treatment approach should be considered for patients with excellent performance status and castration-sensitive disease in light of their expected longer survival. Further studies are warranted to identify the predictors for radiotherapy response in this population.

Neoadjuvant short-course radiotherapy or chemoradiation plus consolidative chemotherapy followed by radical operation for locally advanced rectal cancer.

Introduction: Limited evidence compares short-course radiotherapy (SCRT) and long-course chemoradiotherapy (LCCRT), both of which are followed by consolidative chemotherapy before radical rectal surgery. We conducted a retrospective cohort study to assess treatment response, survival outcomes, and toxicity in patients with locally advanced rectal cancer. Materials and methods: Patients (cT3-4 and/or N+) treated with SCRT or LCCRT, consolidative chemotherapy, or total mesorectal excision between 2013 and 2021 were identified. the cause-specific cumulative incidence of disease-related treatment failure, locoregional recurrence, distant metastases, and overall survival were evaluated using flexible parametric competing risk analysis and Kaplan-Meier methods, adjusted for treatment regimens and clinicopathological factors. A pathological complete response (pCR), tumor downstaging, and toxicity have been reported. Results: Among the 144 patients, 115 (80%) underwent curative rectal surgery. The LCCRT and SCRT groups achieved pCR in 10 (18%) and seven (12%) patients, respectively (odds ratio, 1.68; 95% confidence interval [CI], 0.59-4.78). The adjusted cause-specific hazard ratio for disease-related treatment failure with LCCRT versus SCRT was 0.26 (95% CI, 0.08-0.87). Three-year cumulative probability of disease-related treatment failure was 10.0% and 25.6% for LCCRT and SCRT, respectively. No significant differences in T-downstaging, N-downstaging, significant pathologic downstaging (ypT0-2N0), locoregional failure, distant metastasis, or overall survival were found. Late rectal toxicity occurred in 10 (15%) LCCRT and two (3%) SCRT patients, respectively. Conclusion: LCCRT with consolidative chemotherapy demonstrated improved disease-related treatment failure compared with SCRT, despite higher late rectal toxicity. Further research is needed to assess the long-term oncologic outcomes and toxicity.