Co-enrichment of cancer-associated bacterial taxa is correlated with immune cell infiltrates in esophageal tumor tissue.

Esophageal carcinoma (ESCA) is a leading cause of cancer-related death worldwide, and certain oral and intestinal pathogens have been associated with cancer development and progression. We asked if esophageal microbiomes had shared alterations that could provide novel biomarkers for ESCA risk. We extracted DNA from tumor and non-tumor tissue of 212 patients in the NCI-MD case control study and sequenced the 16S rRNA gene (V3-4), with TCGA ESCA RNA-seq (n = 172) and WGS (n = 123) non-human reads used as validation. We identified four taxa, Campylobacter, Prevotella, Streptococcus, and Fusobacterium as highly enriched in esophageal cancer across all cohorts. Using SparCC, we discovered that Fusobacterium and Prevotella were also co-enriched across all cohorts. We then analyzed immune cell infiltration to determine if these dysbiotic taxa were associated with immune signatures. Using xCell to obtain predicted immune infiltrates, we identified a depletion of megakaryocyte-erythroid progenitor (MEP) cells in tumors with presence of any of the four taxa, along with enrichment of platelets in tumors with Campylobactor or Fusobacterium. Taken together, our results suggest that intratumoral presence of these co-occurring bacterial genera may confer tumor promoting immune alterations that allow disease progression in esophageal cancer.

Feasibility of abdominal fat quantification on MRI and impact on effectiveness of abdominal compression for radiotherapy motion management.

The impact of fat on abdominal compression effectiveness in abdominal cancers was determined using magnetic resonance imaging (MRI). Visceral and subcutaneous fat were delineated on T2W 3D MRI, and motion change with compression was measured on 2D cine MRI. Results from 16 participants showed no correlation between fat percentage, body mass index (BMI), and motion change. Median BMI was 28.7 (SD, 4.9). Mean motion reduction was 7.8 mm (IQR, 5.0; p = 0.001) with compression. While no direct link was found between fat, BMI, and compression effectiveness, abdominal compression remains crucial for motion management in radiotherapy planning, providing dosimetric benefits.

Acute Toxicity of Hypofractionated and Conventionally Fractionated (Chemo)Radiotherapy Regimens for Bladder Cancer: An Exploratory Analysis from the RAIDER Trial.

AIMS: Adding concurrent (chemo)therapy to radiotherapy improves outcomes for muscle-invasive bladder cancer patients. A recent meta-analysis showed superior invasive locoregional disease control for a hypofractionated 55 Gy in 20 fractions schedule compared with 64 Gy in 32 fractions. In the RAIDER clinical trial, patients undergoing 20 or 32 fractions of radical radiotherapy were randomised (1:1:2) to standard radiotherapy or to standard-dose or escalated-dose adaptive radiotherapy. Neoadjuvant chemotherapy and concomitant therapy were permitted. We report exploratory analyses of acute toxicity by concomitant therapy-fractionation schedule combination. MATERIALS AND METHODS: Participants had unifocal bladder urothelial carcinoma staged T2-T4a N0 M0. Acute toxicity was assessed (Common Terminology Criteria for Adverse Events) weekly during radiotherapy and at 10 weeks after the start of treatment. Within each fractionation cohort, non-randomised comparisons of the proportion of patients reporting treatment emergent grade 2 or worse genitourinary, gastrointestinal or other adverse events at any point in the acute period were carried out using Fisher's exact tests. RESULTS: Between September 2015 and April 2020, 345 (163 receiving 20 fractions; 182 receiving 32 fractions) patients were recruited from 46 centres. The median age was 73 years; 49% received neoadjuvant chemotherapy; 71% received concomitant therapy, with 5-fluorouracil/mitomycin C most commonly used: 44/114 (39%) receiving 20 fractions; 94/130 (72%) receiving 32 fractions. The acute grade 2+ gastrointestinal toxicity rate was higher in those receiving concomitant therapy compared with radiotherapy alone in the 20-fraction cohort [54/111 (49%) versus 7/49 (14%), P < 0.001] but not in the 32-fraction cohort (P = 0.355). Grade 2+ gastrointestinal toxicity was highest for gemcitabine, with evidence of significant differences across therapies in the 32-fraction cohort (P = 0.006), with a similar pattern but no significant differences in the 20-fraction cohort (P = 0.099). There was no evidence of differences in grade 2+ genitourinary toxicity between concomitant therapies in either the 20- or 32-fraction cohorts. CONCLUSION: Grade 2+ acute adverse events are common. The toxicity profile varied by type of concomitant therapy; the gastrointestinal toxicity rate seemed to be higher in patients receiving gemcitabine.

Effect of Race and Ethnicity on Risk of Radiotherapy Toxicity and Implications for Radiogenomics.

AIMS: Patient factors affect the risk of radiotherapy toxicity, but many are poorly defined. Studies have shown that race affects cancer incidence, survival, drug response, molecular pathways and epigenetics. Effects on radiosensitivity and radiotherapy toxicity are not well studied. The aim of the present study was to identify the effects of race and ethnicity on the risk of radiotherapy toxicity. MATERIALS AND METHODS: A systematic review was carried out of PubMed, Ovid Medline and Ovid Embase with no year limit. PRISMA 2020 guidelines were followed. Two independent assessors reviewed papers. RESULTS: Of 607 papers screened, 46 fulfilled the inclusion criteria. Papers were published between 1996 and 2021 and involved 30-28,354 individuals (median 433). Most involved patients with prostate (33%), breast (26%) and lung (9%) cancer. Both early and late toxicities were studied. Some studies reported a higher risk of toxicity in White men with prostate cancer compared with other races and ethnicities. For breast cancer patients, some reported an increased risk of toxicity in White women compared with other race and ethnic groups. In general, it was difficult to draw conclusions due to insufficient reporting and analysis of race and ethnicity in published literature. CONCLUSIONS: Reporting of race and ethnicity in radiotherapy studies must be harmonised and improved and frameworks are needed to improve the quality of reporting. Further research is needed to understand how ancestral heritage might affect radiosensitivity and risk of radiotherapy toxicity.

Using Real-world Data to Define a Validated Nomogram for Advanced Bladder Cancer Patients Who Respond to Immunotherapy.

AIMS: Immune checkpoint inhibitors (ICIs) are used in incurable urothelial cancers, both in chemo-naïve and platinum-refractory patients. Efficacy and toxicity data published outside controlled clinical trials are limited. We report overall survival, progression-free survival and toxicities of ICIs in locally advanced (LABC) or metastatic bladder cancer (MBC). We aimed to develop and validate a prognostic model for these patients. MATERIALS AND METHODS: A multicentre real-world individual patient-level data study (n = 272) evaluating ICIs in the first-line platinum-ineligible or platinum-refractory setting for LABC/MBC between March 2017 and February 2020 was undertaken. Cox regression analyses evaluated the association of prognostic factors with overall survival. Data were split to create a training (n = 208) and validation (n = 64) cohort. The backward elimination method with a P-value cut-off of 0.05 was used to develop a reduced prognostic model using the training data set. The concordance index and assessment of observed versus predicted survival probabilities were used to evaluate the final model. RESULTS: The median follow-up was 18.9 (15.8-21.5) months. The median overall survival and progression-free survival in the training cohort were 9.2 (95% confidence interval 7.4-10.5) and 4.5 months (3.5-5.7), respectively. The most common grade 1/2 adverse events recorded were fatigue (47.8%) and infection (19.9%). Five key prognostic factors found in the training set were low haemoglobin, high neutrophil count, choice of immunotherapy favouring pembrolizumab, presence of liver metastasis and steroid use within 30 days of treatment. The concordance index for the training and validation cohorts was 0.66 (standard error = 0.05) and 0.64 (standard error = 0.04), respectively, for the final model. A nomogram was developed to calculate the expected survival probabilities based on risk factors. CONCLUSIONS: Real-world data were used to produce a validated prognostic model for overall survival in LABC/MBC treated with ICIs. This model could assist in patient stratification, interpreting and framing future trials incorporating PD-1/PD-L1 inhibitors in LABC/MBC.

Translation of Prognostic and Pharmacodynamic Biomarkers from Trial to Non-trial Patients with Metastatic Castration-resistant Prostate Cancer Treated with Docetaxel.

AIMS: We conducted a pooled analysis of four randomised controlled trials and a non-trial retrospective dataset to study the changes in serum prostate-specific antigen (PSA) concentrations during treatment and its impact on survival in men treated with docetaxel for metastatic castration-resistant prostate cancer. We also compared the outcomes and pre-treatment prognostic factors between trial and non-trial patients. MATERIALS AND METHODS: Data were obtained from four randomised controlled trials and a non-trial cohort from a tertiary cancer centre. The PSA kinetics covariates chosen were absolute value (PSAT), best percentage change (BPCH) and tumour growth rate (K). The association between the covariates collected and overall survival was assessed within a Cox proportional hazards model. How well a covariate captured the difference between trial and non-trial patients was assessed by reporting on models with or without trial status as a covariate. RESULTS: We reviewed individual datasets of 2282 patients. The median overall survival for trial patients was 20.4 (95% confidence interval 19.6-22.2) months and for the non-trial cohort was 12.4 (10.7-14.7) months (P < 0.001). Of the pre-treatment factors, we found that only lactate dehydrogenase fully captured the difference in prognosis between the trial and non-trial cohorts. All PSA kinetic metrics appeared to be prognostic in both the trial and non-trial patients. However, the effect size was reduced in non-trial versus trial patients (interaction P < 0.001). Of the time-dependent covariates, we found that BPCH best captured the difference between trial and non-trial patient prognosis. CONCLUSIONS: The analysis presented here highlights how data from open-source trial databases can be combined with emerging clinical practice databases to assess differences between trial versus non-trial patients for particular treatments. These results highlight the importance of developing prognostic models using both pre-treatment and time-dependent biomarkers of new treatments.

Changes in Magnetic Resonance Imaging Radiomic Features in Response to Androgen Deprivation Therapy in Patients with Intermediate- and High-risk Prostate Cancer.

AIMS: The benefits of neoadjuvant androgen deprivation therapy (nADT) in the management of intermediate- and high-risk prostate cancer patients have been well-established. The aim of this study was to identify radiomic prognostic features derived from routine anatomic magnetic resonance imaging (MRI) sequences that can predict the response of the prostate cancer to nADT. MATERIALS AND METHODS: Patients with intermediate- and high-risk prostate cancer (with one of clinical stage ≥ T2c, Gleason score ≥7 or presenting prostate-specific antigen ≥10) who received 3 months of ADT prior to radical external beam radiotherapy were enrolled into this study. The relative blood volume and the relative blood flow were used as dynamic MRI kinetic parameters to quantify vascular changes as responses to nADT. For all pre- and post-nADT data sets, a combination of T2-weighted and contrast-enhanced T1-weighted anatomic images were used to define regions of interest (ROI) as the dominant malignant nodules (DMNs) and the benign prostate (the entire prostate with the summed DMNs being subtracted). MRI textural radiomic features associated with prostate cancer response in the literature of energy and homogeneity were selected. Pyradiomics was used to extract textural features of the ROIs. A Wilcoxon signed-rank test was carried out to investigate if there were statistically significant differences in values of radiomic features between: (i) benign prostate ROI and DMN pre-nADT; (ii) pre- and post-nADT of benign prostate ROI; (iii) pre- and post-nADT of DMN. Changes in radiomic features and dynamic MRI kinetic parameters were correlated using the Spearman correlation test. RESULTS: Twenty prostate cancer patients were recruited into the study. The median time between the first baseline scan and the first on-treatment scan was 91.5 days (range 82-105). One patient had no discernible tumour visible, leaving 19 patients with evaluable data for the analysis. Baseline homogeneity and energy values differed significantly between benign and malignant tissue (P < 0.01). In response to nADT, homogeneity and energy showed reciprocal changes, significantly increased in benign prostate while decreasing in the DMN. The reduction in tumour homogeneity and energy feature values showed a positive association with the decline in tumour blood flow and tumour blood volume induced by androgen deprivation as derived from dynamic MRI parameters. CONCLUSION: Energy and homogeneity radiomic features derived from MRI of benign and malignant prostate showed significant reciprocal changes in response to nADT. This study confirms the potential of these radiomic features to act as surrogate markers of tumour androgen sensitivity due to their strong association with ADT-induced physiological effects in prostate tumours.

Response evaluation of locoregional therapies in combined hepatocellular-cholangiocarcinoma and intrahepatic cholangiocarcinoma versus hepatocellular carcinoma: a propensity score matched study.

AIM: To evaluate the response of locoregional therapy (LRT) on combined hepatocellular-cholangiocarcinoma (cHCC-CC) and intrahepatic cholangiocarcinoma (IHC) and compare their outcomes with propensity matched hepatocellular carcinoma (HCC) patients. MATERIALS AND METHODS: From January 2011 to July 2020, 13 patients with cHCC-CC (11 men, two women, median age 56 years) and 15 IHC patients (10 men, five women, median age 60 years) were compared with 101 HCC patients (79 men, 22 women, median age 60 years) after LRT. All tumours were proven histologically. Among the 13 cHCC-CC patients, 11 received transarterial chemoembolisation (TACE), one received microwave ablation (MWA) and one received TACE with radiofrequency ablation (RFA). Of 15 IHC patients, eight received TACE, five received RFA, and one received MWA, and one received TACE with RFA. Propensity score matching (PSM) was done with conditional logistic regression adjusted for age, type of LRT, tumour specific features and Child-Pugh score. RESULTS: After LRT, on univariate analysis an objective response was seen in 30% of cHCC-CC and 53% of IHC patients. PSM analysis demonstrated shorter progression-free survival (PFS; cHCC-CC versus HCC: 1.5 versus 7.5 months; IHC versus HCC: 6 versus 14 months, p<0.05), overall survival (OS; cHCC-CC versus HCC: 12 versus 28 months; IHC versus HCC: 18 versus 34 months, p<0.005), and poor objective response (cHCC-CC versus HCC: 25% versus 91%; IHC versus HCC: 58% versus 88%, p<0.05) in cHCC-CC and IHC patients versus HCC patients. Hypovascular tumour, macrovascular invasion, and infiltrative appearance were independent prognostic factors for OS in IHC patients. CONCLUSION: cHCC-CC and IHC are aggressive tumours with a poor objective response, greater distant progression of the disease and shorter PFS and OS post LRT as compared to HCC.

Outcomes of ketorolac versus depomedrol infiltrations for subacromial impingement syndrome: a randomized controlled trial.

PURPOSE: Local subacromial infiltration with steroids is a common method of treatment of subacromial impingement syndrome. However, the use of steroids has concerns like tendon rupture, articular cartilage changes and infections. Local NSAIDs infiltration has recently been tried in literature. This study compares the effect of subacromial injections of ketorolac with steroids. METHODS: A randomized controlled study was planned with 35 patients in each group. Patients in group-1 were infiltrated with subacromial ketorolac (60 mg with 2% lignocaine) and in group-2 with a steroid (methylprednisolone-40 mg with 2% lignocaine). A similar rehabilitation protocol was followed, and clinical outcomes were analyzed using visual analog scale (VAS) for pain and shoulder pain and disability score (SPADI) and range of motion at one-month and three-months follow-up. RESULTS: Total data of 67 patients were analyzed, as three patients were lost to follow-up. In group 1, mean VAS improved from 7.9 [Formula: see text] 0.95 to 3.19 [Formula: see text] 0.81 (p < 0.001) and SPADI improved from 61.41 [Formula: see text] 11.86 to 28.91 [Formula: see text] 9.06 (p < 0.001) at three months, respectively. In group 2, mean VAS improved from 8.05 [Formula: see text] 0.94 to 2.9 [Formula: see text] 0.64 (p < 0.001) and SPADI improved from 63.45 [Formula: see text] 9.64 to 25.32 [Formula: see text] 6.87 (p < 0.001) at three months, respectively. However, there were no differences in functional outcomes between the groups (p = 0.21 for VAS, p = 0.16 for SPADI). CONCLUSION: Subacromial ketorolac infiltration has an equivalent outcome as that of steroid infiltration. Ketorolac could be considered as a reasonable alternative to steroids in cases where it is contraindicated.

Curative-Intent Radiotherapy for Squamous Cell Carcinoma of the Head and Neck in Sri Lanka: The Impact of Radiotherapy Technique on Survival.

AIMS: We conducted a retrospective analysis of patients with squamous cell carcinoma of the head and neck (SCCHN) treated with curative-intent radiotherapy at the National Cancer Institute of Sri Lanka to determine the impact of the treatment technique on disease-free survival (DFS). MATERIALS AND METHODS: SCCHN patients treated with radical radiotherapy or adjuvant postoperative radiotherapy from 2016 to 2017 were included in the study. Data on the following variables were collected by reviewing clinical and radiotherapy treatment records: age, gender, tumour site, stage, time to delivery of radiotherapy, use of neoadjuvant chemotherapy, use of concurrent radiosensitising chemotherapy and treatment technique. DFS, defined as the time to death, tumour recurrence or loss to follow-up, was the primary end point and outcomes were compared between patients treated with intensity-modulated radiotherapy (IMRT) in linear accelerators and those treated with conventional radiotherapy in cobalt teletherapy units. Univariate and multivariate analyses were carried out on known prognostic variables. RESULTS: In total, 408 patients were included in the study, with 138 (34%) being treated with IMRT in the linear accelerator. More than 75% of patients were of stage III or IV at diagnosis. The 2-year DFS of the whole cohort was 25% (95% confidence interval 21-30%). Patients treated with IMRT in the linear accelerator had a superior DFS in comparison with those treated with conventional radiotherapy in the cobalt teletherapy units (P < 0.001, hazard ratio 0.64, 95% confidence interval 0.5-0.82). Higher stage, cobalt treatment and use of neoadjuvant chemotherapy were adversely associated with DFS on multivariate analysis. CONCLUSION: A large proportion of patients with SCCHN treated with curative-intent radiotherapy in Sri Lanka had locally advanced disease and DFS was superior in patients treated with IMRT in the linear accelerator.

A practical approach to bladder preservation with hypofractionated radiotherapy for localised muscle-invasive bladder cancer.

Bladder preservation with trimodality treatment (TMT) is an alternative strategy to radical cystectomy (RC) for the management of localised muscle invasive bladder cancer (MIBC). TMT comprises of transurethral resection of the bladder tumour (TURBT) followed by radiotherapy with concurrent radiosensitisation. TMT studies have shown neo-adjuvant chemotherapy with cisplatin-based regimens is often given to further improve survival outcomes. A hypofractionated radiotherapy regimen is preferable due to its non-inferiority in local control and late toxicities. Radiosensitisation can comprise concurrent chemotherapy (with gemcitabine, cisplatin or combination fluorouracil and mitomycin), CON (carbogen and nicotinomide) or hyperthermic treatment. Radiotherapy techniques are continuously improving and becoming more personalised. As the bladder is a mobile structure subject to volumetric changes from filling, an adaptive approach can optimise bladder coverage and reduce dose to normal tissue. Adaptive radiotherapy (ART) is an evolving field that aims to overcome this. Improved knowledge of tumour biology and advances in imaging techniques aims to further optimise and personalise treatment.

Evaluation of Surgical Correction of Adolescent Idiopathic Scoliosis by Transpedicular Screws and Rods.

Transpedicular screw fixation is a challenging procedure for the correction of deformity of Adolescent Idiopathic Scoliosis (AIS) in the dorso-lumbar spine. The inadvertently misplaced screws have a high risk of complications. The exactness of the pedicle screws is normally distinct as the screws axis being fully enclosed within the cortices of the pedicle. Evaluation of the surgical correction of adolescent idiopathic scoliosis by transpedicular screws and rods was done in single posterior dynamic approach. This prospective observational study was conducted in the National Institute of Traumatology and Orthopedic Rehabilitation, Dhaka and different Hospitals in Dhaka, Bangladesh from July 2015 to March 2017. Ten patients at the age >9 years and <19 years who were admitted with a diagnosis of AIS during the period of study. The pedicle is a power nucleus of the vertebra and offers a secure grip of all 3 columns. Pedicle screw instrumentation has advantages of rigid fixation with improved 3D correction and it has been accepted as a reliable method with a high margin of safety. Accurate placement of the pedicle screws is important to reduce possible irreversible complication. So, all cases were corrected by transpedicular screws and rods in single posterior approach. In every case fusion was done in selected segments. In this study out of 10 patients 7(70.0%) were 10 to 14 years of age and 3(30.0%) were 15 to 18 years. Mean age 9.51±2.13 years. Minimum 10 years and maximum 18 years. Majority 7(70.0%) of the patients were female and the rest 3(30.0%) male. Five (50.0%) presented with level of involvement, 3(30.0%) patients thoracic and 2(20.0%) patients had lumbar. Maximum 7(70.0%) presented right sided involvement and rest 3(30.0%) left sided involvement. Before surgical intervention 100% patients had rib hump and positive Adams forward bending test, 70.0% patients had asymmetry of shoulder and uneven hip and also 50% patients had pain. After surgical treatment with transpedicular screws and rods through posterior approach, 70% of patients improved in terms of deformity. The average major curve deformity as defined by Cobb angle measurements was measured to be 54.9°±9.9° (40°-68°) in pre-surgery. After surgery this deformity corrected to 16.0°±4.9° (10°-24°) on average as measured in erect posture posterior anterior and lateral view. This represents significant improvement average of 71.4±4.3% (64.6-75.09) (p<0.001). This correction was maintained at 24 months after surgery. Functional results assessed by Modified Macnab criteria, significant number of 7(70.0%) patients had excellent outcome, 2(20.0%) patients had good outcome, 1(10.0%) patients had fair outcome and no poor outcome. Ninety percent (90%) patients had satisfactory results. No patient deteriorates neurologically after surgery. It is concluded that satisfactory curve correction and maintenance thereof is possible in adolescent idiopathic scoliosis, with posterior instrumentation by transpedicular screw and rods with effective reduction of cost and associated risks.

Changes in pain catastrophization and neuropathic pain following operative stabilisation for patellofemoral instability: a prospective study with twelve month follow-up.

PURPOSE: To determine the prevalence and change in neuropathic pain or pain catastrophizing before and 12 months following patellar stabilisation surgery for patellofemoral instability. METHODS: We conducted a prospective clinical audit within a UK NHS orthopaedic surgical centre. Data from 84 patients with patellofemoral instability requiring stabilisation were analysed. Fifty percent (42/84) underwent MPFL reconstruction alone, and 16% (13/84) had both trochleoplasty and MPFL reconstruction. Neuropathic pain was assessed using painDETECT score. Pain catastrophizing was assessed using the Pain Catastrophizing Score. The Norwich Patellar Instability (NPI) Score and Kujala Patellofemoral Disorder Score were also routinely collected pre-operatively and one year post-operatively. RESULTS: At 12 months post-operatively there was a statistically significant reduction in mean Pain Catastrophizing Scores (18.9-15.7; p < 0.02), but no change in mean painDETECT scores (7.3-7.8; p = 0.72). There was a statistically significant improvement in NPI scores (90.2-61.9; p < 0.01) and Kujala Patellofemoral Disorder Scores (48.7-58.1; p = 0.01). The prevalence of pain catastrophizing decreased from 31% pre-operatively to 24% post-operatively, whereas the prevalence of neuropathic pain remained consisted (10-11%). CONCLUSIONS: Neuropathic pain and catastrophizing symptoms are not commonly reported and did not significantly change following patellofemoral stabilisation surgery. Whilst low, for those affected, there remains a need to intervene to improve outcomes following PFI surgery.

Short Segment Pedicle Screw Fixation Including Fracture Vertebrae for the Management of Unstable Thoracolumbar Burst Fracture.

Stabilization procedures for the treatment of thoracolumbar burst fractures remain controversial. Traditional stabilization procedures include short and long segment stabilization. Nowadays short-segment including fracture vertebrae stabilization is one of the modalities of treatment. This study aimed to analyze the radiological and functional outcome of the Short-segment fixation with the inclusion of the fracture level (SSFIFL) for the treatment of unstable thoracolumbar fractures. In this prospective study, 40 cases of thoracolumbar burst fractures with incomplete spinal cord injury were operated by SSFIFL from Jan 2016 to Jan 2019 in NITOR, Dhaka, Bangladesh. The mean follow-up period was 18 months. Pre-operative and post-operative radiological parameters were the kyphotic angle, kyphotic deformation, Beck index, and clinical parameters include ASIA impairment scale, Visual Analogue Scale (VAS), and Oswestry Disability Index (ODI). Mean age was 32.30±11.85 years, among whom 80% (32) were male in this study. Fall from height (85%) was the main cause and occurs mostly in day labors (45%). Most common skeletal level was L1 (52.5%) followed by L2 (32.5%). Most cases operated between 10-15 days with mean duration of 119.58±19.93 minutes and mean blood loss of 350.38±31.26ml. The pre-operative kyphotic angle was 22.75±4.53° and 9.13±3.04° at final follow-up with correction loss of 5.15±2.54° (p<0.05). Most of the patients were in ASIA-C grade (57.5%) pre-operatively and ASIA-E (67.5%) at final follow-up after surgery (p=0.001). ODI improved from 67.20±12.90 to 25.08±11.36 and VAS form 60.25±8.91 to 21.50±8.33 (p<0.05). Main complication was superficial infection (5 cases) followed by bent rod and CSF leakage in 2 cases each. Good radiological and clinical outcome can be achieved by inclusion of fracture level in a short-segment fixation for unstable thoracolumbar fractures. Finally, this technique may allow us to save two or more segments of vertebral motion.

Variations in Demand across England for the Magnetic Resonance-Linac Technology, Simulated Utilising Local-level Demographic and Cancer Data in the Malthus Project.

AIMS: Cancer incidence varies across England, which affects the local-level demand for treatments. The magnetic resonance-linac (MR-linac) is a new radiotherapy technology that combines imaging and treatment. Here we model the demand and demand variations for the MR-linac across England. MATERIALS AND METHODS: Initial clinical indications were provided by the MR-linac consortium and introduced into the Malthus radiotherapy clinical decision trees. The Malthus model contains Clinical Commissioning Group (CCG) population, cancer incidence and stage presentation data (for lung and prostate) and simulated the demand for the MR-linac for all CCGs and Radiotherapy Operational Delivery Networks (RODN) across England. RESULTS: Based on the initial target clinical indications, the MR-linac could service 16% of England's fraction burden. The simulated fractions/million population demand/annum varies between 3000 and 10 600 fractions/million at the CCG level. Focussing only on the cancer population, the simulated fractions/1000 cancer cases demand/annum ranges from 1028 to 1195 fractions/1000 cases. If a national average for fractions/million demand was then used, at the RODN level, the variation from actual annual demand ranges from an overestimation of 8400 fractions to an underestimation of 5800 fractions. When using the national average fractions/1000 cases, the RODN demand varies from an overestimation of 3200 fractions to an underestimation of 3000 fractions. CONCLUSIONS: Planning cancer services is complex due to regional variations in cancer burden. The variations in simulated demand of the MR-linac highlight the requirement to use local-level data when planning to introduce a new technology.

Hypoxia and its Modification in Bladder Cancer: Current and Future Perspectives.

Radiotherapy plays an essential role in the curative treatment of muscle-invasive bladder cancer (MIBC). Hypoxia affects the response to MIBC radiotherapy, limiting radiocurability. Likewise, hypoxia influences MIBC genetic instability and malignant progression being associated with metastatic disease and a worse prognosis. Hypoxia identification in MIBC enables treatment stratification and the promise of improved survival. The most promising methods are histopathological markers such as necrosis; biomarkers of protein expression such as HIF-1α, GLUT-1 and CAIX; microRNAs; and novel mRNA signatures. Although hypoxia modification can take different forms, the gold standard remains carbogen and nicotinamide, which improve local control rates in bladder preservation and absolute overall survival with no significant increase in late toxicity. This is an exciting time for evolving therapies such as bioreductive agents, novel oxygen delivery techniques, immunotherapy and poly (ADP-ribose) polymerase 1 (PARP) inhibitors, all in development and representing upcoming trends in MIBC hypoxia modification. Whatever the future holds for hypoxia-modified radiotherapy, there is no doubt of its importance in MIBC. mRNA signatures provide an ideal platform for the selection of those with hypoxic tumours but are yet to qualified and integrated into the clinic. Future interventional trials will require biomarker stratification to ensure optimal treatment response to improve outcomes for patients with MIBC.

Clinical Guidance for the Management of Patients with Urothelial Cancers During the COVID-19 Pandemic - Rapid Review.

The current COVID-19 pandemic presents a substantial obstacle to cancer patient care. Data from China as well as risk models suppose that cancer patients, particularly those on active, immunosuppressive therapies are at higher risks of severe infection from the illness. In addition, staff illness and restructuring of services to deal with the crisis will inevitably place treatment capacities under significant strain. These guidelines aim to expand on those provided by NHS England regarding cancer care during the coronavirus pandemic by examining the known literature and provide guidance in managing patients with urothelial and rarer urinary tract cancers. In particular, they address the estimated risk and benefits of standard treatments and consider the alternatives in the current situation. As a result, it is recommended that this guidance will help form a framework for shared decision making with patients. Moreover, they do not advise a one-size-fits-all approach but recommend continual assessment of the situation with discussion within and between centres.