Metabolic Tumour Volume as a Predictor of Survival for Sinonasal Tract Squamous Cell Carcinoma

Background: High uptake of F18-fluorodeoxyglucose parameters for glucose metabolism is related to shorter survival in sinonasal tract cancer with various histological classifications. We investigated whether F18-fluorodeoxyglucose uptake parameters are associated with survival outcomes for patients with only squamous cell carcinoma (SCC) in the sinonasal tract that are treated either with surgery or nonsurgery. Methods: We retrospectively observed F18-fluorodeoxyglucose uptake parameters on positron emission tomography with computed tomography for the primary tumour of SCC in 39 patients. Log-rank test or a Cox regression model with 95% confidence interval (95%CI) and hazard ratio (HR) were used for monovariable or multivariable analysis, respectively. We determined cut-off values of the F18-fluorodeoxyglucose uptake parameters using the lowest p value for monovariable sinonasal tract cancer-specific survival analysis. Results: Monovariable analysis showed that patients with metabolic tumour volume (MTV) ≥ 21.8 had a shorter cancer-specific, disease-free and local recurrence-free survival than those with MTV < 21.8. After adjusting for age, gender, clinical stage and treatment group in the multivariable analysis, MTV (≥21.8/<21.8) was related to shorter cancer-specific (HR: 3.69, 95%CI: 1.17–12.0), disease-free (HR: 3.38, 95%CI: 1.19–9.71) and local recurrence-free (HR: 5.42, 95%CI: 1.59–20.3) survivals. Conclusions: MTV as advances in diagnostics of sinonasal tract SCC is a predictor.

Recurrence rate of sphenoid wing meningiomas and role of peritumoural brain edema: a single center retrospective study

Objective: To evaluate the recurrence rate of the operatively treated sphenoid wing meningiomas (SWMs) in relation to other factors and role of PTBE in recurrence as a prognostic factors in a series of 67 patients. Materials and methods: The magnetic resonance imaging (MRI), and pathology data for 67 patients with SWM, who underwent surgery at Uzhhorod Regional Neurosurgical Center between 2007 and 2021 were examined. The recurrence rate and role of PTBE in recurrence in relation to: gender, age, extend of resection, histopathology, tumor volume, location and time of recurrence were evaluated. Follow-up period ranged from 6 to 168 months (median, 87 months) after surgical resection. Results: In our study, the mean age of patients is 47 years, ranged (20-74), at the average (53.5). Male 16 (23.9%), female 51 (76.1%). Mean tumor volume was (32.8cm3), ranged 4.2cm3-143.7cm3. Edema Index (EI) 1; 27 (40.3%) absent edema, and (EI) >1; in 40 (59.7%) present edema. Recurrence rate was 11 (16.4%) patients, 8 (20.0%) patients with PTBE, as compared to 3 (11.1%) patients without PTBE, (p=0,50). Female (8 patients, 15.7%), male (3 patients, 18.7%). The mean age of recurrence was 50.9 years, ranged (21-75), at the average 52.0 years. The mean age in female was 50.8 years, in male 51.0. Bivariate analysis of simultaneous effect of gender and age on SWM recurrence with logistic regression yield both main effect and interaction effect (β gender=M=7.56±6.44, P=0.24; β age=-0.034±0.031, p=0.28; β interaction term=-0.13±0.12, p=0.26). Out of 11 recurrence cases, (2 cases, 9.5%) with small tumour volume, (5 cases, 15.6%) with medium, (3 cases, 33.3%) with large, and (one case, 20.0%) with giant tumour volume. The effect of tumour volume on recurrence rate is insignificant, χ2=2.42, p=0.49.Location of SWM; the recurrence was in (6 cases, 25.0%) of CM location, (2 cases, 25.0%) of SOM and (3 cases, 11.5%) in lateral SWM, (p=0.19). Pathological grade, in the low grade (Gr.I) 7 recurrence cases (13.0%), as compared to 4cases (44.4%) in atypical Gr II, (p=0.01). Simpson grade, the recurrence rate was; 0% in Gr. I; 13.9% in Gr. II; 20.0% in Gr.III; and 33.3% in Gr. IV and 3 cases had died in the early post op (p<0.05). Conclusion: The factors which had a strong impact on the recurrence rate in our study,; i) pathological grade (Gr. II, atypical type) p=0.01 and ii) Simpson grade (extend of tumor resection, p<0.05), while, PTBE (P=0.50), tumor volume (χ2=2.42, p=0.49) and location (χ2=3.37, p=0.19), are weak and non strong factors for recurrence. However, time of recurrence is shorter in patients with PTBE (W=20.5, p=0.092). WHO Gr. II (Spearman’s p=-0.86, p=0.00063) and negligible for Simpson grade (Spearman’s=-0.15, p=0.66).

Refractory Craniopharyngioma: Successful Treatment with LINAC Based Stereotactic Radiosurgery(SRS): First Case in Nepal

Purpose: To present first case of refractory craniopharyngioma treated successfully with SRS in Nepal.Background: Craniopharyngioma is a benign tumour, which progresses slowly and compresses the pituitary gland and nearby structures. First line of treatment is surgery followed by adjuvant radiotherapy as complete resection is usually not feasible. Here, we are reporting a case of recurrent craniopharyngioma treated with LINAC based SRS.Case Presentation: A 43 years old man diagnosed case of craniopharyngioma in May 2019. He underwent left pterional craniotomy and subtotal resection of tumour and kept on observation. He developed symptomatic as well as radiological recurrence in July 2020. Second debulking was not possible, so we did SRS on 23rd August 2020; 14Gy Dose was delivered to gross tumour volume. Six months after SRS, Patient is doing well.Conclusions: LINAC based SRS is a frameless, non-invasive and safe procedure with excellent clinical outcomes for recurrent or residual craniopharyngioma.

Hyaluronic Acid-Conjugated Carbon Nanomaterials for Enhanced Tumour Targeting Ability

Hyaluronic acid (HA) has been implemented for chemo and photothermal therapy to target tumour cells overexpressing the CD44+ receptor. HA-targeting hybrid systems allows carbon nanomaterial (CNM) carriers to efficiently deliver anticancer drugs, such as doxorubicin and gemcitabine, to the tumour sites. Carbon nanotubes (CNTs), graphene, graphene oxide (GO), and graphene quantum dots (GQDs) are grouped for a detailed review of the novel nanocomposites for cancer therapy. Some CNMs proved to be more successful than others in terms of stability and effectiveness at removing relative tumour volume. While the literature has been focused primarily on the CNTs and GO, other CNMs such as carbon nano-onions (CNOs) proved quite promising for targeted drug delivery using HA. Near-infrared laser photoablation is also reviewed as a primary method of cancer therapy—it can be used alone or in conjunction with chemotherapy to achieve promising chemo-photothermal therapy protocols. This review aims to give a background into HA and why it is a successful cancer-targeting component of current CNM-based drug delivery systems.

The quantitative impact of joint peer review with a specialist radiologist in head and neck cancer radiotherapy planning

Objectives: Radiologist input in peer review of head and neck radiotherapy has been introduced as a routine departmental approach. The aim was to evaluate this practice and to quantitatively analyse the changes made. Methods: Patients treated with radical-dose radiotherapy between August–November 2020 were reviewed. The incidence of major and minor changes, as defined by The Royal College of Radiologists guidance, was prospectively recorded. The amended radiotherapy volumes were compared with the original volumes using Jaccard Index (JI) to assess conformity; Geographical Miss Index (GMI) for under contouring; and Hausdorff Distance (HD) between the volumes. Results: In total 73 out of 87 (84%) patients were discussed. Changes were recommended in 38 (52%) patients: 30 had ≥1 major change, eight had minor changes only. There were 99 amended volumes: The overall median JI, GMI and HD was 0.91 (interquartile range [IQR]=0.80–0.97), 0.06 (IQR = 0.02–0.18) and 0.42 cm (IQR = 0.20–1.17 cm) respectively. The nodal gross-tumour-volume (GTVn) and therapeutic high-dose nodal clinical-target-volume (CTVn) had the biggest magnitude of changes: The median JI, GMI and HD of GTVn was 0.89 (IQR = 0.44–0.95), 0.11 (IQR = 0.05–0.51), 3.71 cm (IQR = 0.31–6.93 cm); high-dose CTVn was 0.78 (IQR = 0.59–0.90), 0.20 (IQR = 0.07–0.31) and 3.28 cm (IQR = 1.22–6.18 cm) respectively. There was no observed difference in the quantitative indices of the 85 ‘major’ and 14 ‘minor’ volumes (p = 0.5). Conclusions: Routine head and neck radiologist input in radiotherapy peer review is feasible and can help avoid gross error in contouring. Advances in knowledge: The major and minor classification may benefit from differentiation with quantitative indices but requires correlation from clinical outcomes.

Association of Sonographic Features of Unifocal Papillary Thyroid Carcinoma With Cervical Lymph Node Metastasis

Background Papillary thyroid carcinoma (PTC) is the most common pathological type of thyroid carcinoma. We aim to evaluate the association of sonographic features of PTC and cervical lymph node metastasis (CLNM) at the initial surgery. Methods Clinical information, ultrasonographic measurements and features for 1335 patients were acquired in data collection. Univariate analysis was performed to test CLNM by 7 independent variables. Receiver operating characteristic (ROC) curve was created to evaluate the diagnostic performance. Results Univariate analysis showed that gland, location, aspect ratio, margin and echogenic foci were independently associated with CLNM metastatic status (P<0.05). Binary linear regression analysis showed that sex, age, tumour maximum diameter and volume, location, margin and echogenic foci were independent correlative factors. The ROC curves were established based on the relevant factors, the AUC of tumour maximum diameter, tumour volume and margin were 0.74, 0.73, and 0.71, respectively. The multiple-variable linear regression model was constructed with AUC of 0.81, specificity of 72.8%, and sensitivity of 75.0%. ANOVA variance analysis for sub-positive groups, tumour maximum diameter, tumour volume, margin and echogenic foci had statistical significance (P<0.05).Conclusion Younger age, male, larger tumour, margin, and echogenic foci were high risk factors for CLNM in PTC. Cross-sectional aspect ratio with value≥1 had higher predictive value for CLNM in patients with larger thyroid tumors.

Metabolic Activity Via 18 F-FDG PET/CT is Predictive of Microsatellite Instability Status In Colorectal Cancer

Purpose: Identification of microsatellite instability high (MSI-H) colorectal cancer (CRC) is crucial for screening patients most likely to benefit from immunotherapy. We aim to investigate whether the metabolic characteristics is related to MSI status and can be used to predict the MSI-H CRC. Methods: A retrospective analysis was conducted on 420 CRC patients who were identified via [18F]fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography(CT) prior to therapy. Maximum standardised uptake (SUVmax), mean standardised uptake (SUVmean), metabolic tumour volume (MTV) and total lesion glycolysis (TLG) of the primary tumour were calculated and compared between MSI-H and microsatellite stability (MSS). Predictive factors of MSI status were selected from metabolic parameters and clinicopathological profiles via a multivariate analysis.Results: Of 420 colorectal cancers, 44 exhibited a high incidence of MSI. Both MTV and TLG were significantly higher in MSI-H group compared with the MSS group (P=0.004 and P=0.010, respectively). Logistic regression analysis indicated that CRC with MSI-H were related to younger age (P=0.013), primary lesion located at right hemi-colon (P<0.001) and larger MTV on PET/CT imaging (P=0.019). MTV more than 32.19 cm3 of colorectal cancer was linked to the presence of MSI (P=0.019). Conclusion: Tumor metabolic burden were higher in MSI-H CRC which may be useful for predicting the MSI status of CRC patient and thus aid in determination of immunotherapy for patients with CRC.

Tigilanol Tiglate-Mediated Margins: A Comparison With Surgical Margins in Successful Treatment of Canine Mast Cell Tumours

Tigilanol tiglate (TT) is a novel small molecule registered as a veterinary pharmaceutical for intratumoural treatment of canine mast cell tumours (MCTs). The drug has a multifactorial mode of action resulting in rapid destruction of the treated tumour by haemorrhagic necrosis and subsequent slough of the necrotic tumour to reveal a tissue deficit that is left to heal by second intention with minimal to no veterinary intervention. Here we introduce the concept of TT-mediated margins, the calculated margin of tissue loss analogous to surgically applied margins to help clinicians conceptualise tissue deficits formed following tumour destruction by TT relative to surgical excision. We used data from 51 dogs that were recurrence-free 12 months after a single administered TT dose into a single target MCT &lt;10 cm3 in volume in a randomised, controlled clinical trial in the USA. We calculated TT-mediated margins based on length of the longest axis of (i) the tumour prior to treatment and (ii) the maximum tissue deficit formed 7–14 days after TT treatment. We compared these TT-mediated margins for each tumour to two surgical approaches to MCT excision in general practise: modified proportional margins (with 2 cm upper limit) and 3 cm fixed margins. For most dogs, TT-mediated margins were less than half the length of the margins calculated for the two surgical approaches in removing the same tumour. There was a trend for TT-mediated margins to increase with increasing tumour volume. Nonetheless, even for the larger tumours in this study (&gt;2 cm3 volume), 50% of TT-mediated margins were less than half the length of the two surgical margins. Eighteen cases were lower limb MCTs, sites often surgically challenging in veterinary practise. On these lower limbs, TT-mediated margins were less than half the length of the corresponding proportional margins in 56% of cases and larger than proportional margins in only two cases. This study suggests that, in many cases, smaller and more targeted margins could be expected when treating MCTs &lt;10 cm3 volume with TT compared with surgical excision. TT-mediated margins are a novel approach to conceptualise tissue deficits after intratumoural TT treatment.

Granzyme B PET Imaging Stratifies Immune Checkpoint Inhibitor Response in Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is a notoriously difficult cancer to treat. The recent development of immune checkpoint inhibitors has revolutionised HCC therapy; however, successful response is only observed in a small percentage of patients. Biomarkers typically used to predict treatment response in other tumour types are ineffective in HCC, which arises in an immune-suppressive environment. However, imaging markers that measure changes in tumour infiltrating immune cells may supply information that can be used to determine which patients are responding to therapy posttreatment. We have evaluated [18F]AlF-mNOTA-GZP, a radiolabeled peptide targeting granzyme B, to stratify response to ICIs in a HEPA 1-tumours, a syngeneic model of HCC. Posttherapy, in vivo tumour retention of [18F]AlF-mNOTA-GZP was correlated to changes in tumour volume and tumour-infiltrating immune cells. [18F]AlF-mNOTA-GZP successfully stratified response to immune checkpoint inhibition in the syngeneic HEPA 1-6 model. FACS indicated significant changes in the immune environment including a decrease in immune suppressive CD4+ T regulatory cells and increases in tumour-associated GZB+ NK+ cells, which correlated well with tumour radiopharmaceutical uptake. While the immune response to ICI therapies differs in HCC compared to many other cancers, [18F]AlF-mNOTA-GZP retention is able to stratify response to ICI therapy associated with tumour infiltrating GZB+ NK+ cells in this complex tumour microenvironment.

Antibody Drug Conjugates in Glioblastoma – Is There a Future for Them?

Glioblastoma (GBM) is an aggressive and fatal malignancy that despite decades of trials has limited therapeutic options. Antibody drug conjugates (ADCs) are composed of a monoclonal antibody which specifically recognizes a cellular surface antigen linked to a cytotoxic payload. ADCs have demonstrated superior efficacy and/or reduced toxicity in a range of haematological and solid tumors resulting in nine ADCs receiving regulatory approval. ADCs have also been explored in patients with brain tumours but with limited success to date. While earlier generations ADCs in glioma patients have had limited success and high toxicity, newer and improved ADCs characterised by low immunogenicity and more effective payloads have shown promise in a range of tumour types. These newer ADCs have also been tested in glioma patients, however, with mixed results. Factors affecting the effectiveness of ADCs to target the CNS include the blood brain barrier which acts as a physical and biochemical barrier, the pro-cancerogenic and immunosuppressive tumor microenvironment and tumour characteristics like tumour volume and antigen expression. In this paper we review the data regarding the ongoing the development of ADCs in glioma patients as well as potential strategies to overcome these barriers to maximise their therapeutic potential.