Local Modalities Research Articles

Targeted immune activation in pediatric solid tumors: opportunities to complement local control approaches.

Surgery or radiation therapy is nearly universally applied for pediatric solid tumors. In many cases, in diverse tumor types, distant metastatic disease is present and evades surgery or radiation. The systemic host response to these local control modalities may lead to a suppression of antitumor immunity, with potential negative impact on the clinical outcomes for patients in this scenario. Emerging evidence suggests that the perioperative immune responses to surgery or radiation can be modulated therapeutically to preserve anti-tumor immunity, with the added benefit of preventing these local control approaches from serving as pro-tumorigenic stimuli. To realize the potential benefit of therapeutic modulation of the systemic response to surgery or radiation on distant disease that evades these modalities, a detailed knowledge of the tumor-specific immunology as well as the immune responses to surgery and radiation is imperative. In this Review we highlight the current understanding of the tumor immune microenvironment for the most common peripheral pediatric solid tumors, the immune responses to surgery and radiation, and current evidence that supports the potential use of immune activating agents in the perioperative window. Finally, we define existing knowledge gaps that limit the current translational potential of modulating perioperative immunity to achieve effective anti-tumor outcomes.

Multi-Functional Boron-Delivery Agents for Boron Neutron Capture Therapy of Cancers.

Boron neutron capture therapy (BNCT) is a binary cancer treatment that involves the irradiation of 10B-containing tumors with low-energy neutrons (thermal or epithermal). The alpha particles and recoiling Li nuclei that are produced in the 10B-capture nuclear reaction are high-linear-energy transfer particles that destroy boron-loaded tumor cells; therefore, BNCT has the potential to be a localized therapeutic modality. Two boron-delivery agents have been used in clinical trials of BNCT in patients with malignant brain tumors, cutaneous melanoma, or recurrent tumors of the head and neck region, demonstrating the potential of BNCT in the treatment of difficult cancers. A variety of potentially highly effective boron-delivery agents have been synthesized in the past four decades and tested in cells and animal models. These include boron-containing nucleosides, peptides, proteins, polyamines, porphyrins, liposomes, monoclonal antibodies, and nanoparticles of various types. The most promising agents are multi-functional boronated molecules and nanoparticles functionalized with tumor cell-targeting moieties that increase their tumor selectivity and contain a radiolabel or fluorophore to allow quantification of 10B-biodistribution and treatment planning. This review discusses multi-functional boron agents reported in the last decade, but their full potential can only be ascertained after their evaluation in BNCT clinical trials.

Effect of Radiotherapy Dose on Outcome in Nonmetastatic Ewing Sarcoma

Radiation therapy (RT) is an integral part of Ewing sarcoma (EwS) therapy. The Ewing 2008 protocol recommended RT doses ranging from 45 to 54 Gy. However, some patients received other doses of RT. We analyzed the effect of different RT doses on event-free survival (EFS) and overall survival (OS) in patients with EwS. The Ewing 2008 database included 528 RT-admitted patients with nonmetastatic EwS. Recommended multimodal therapy consisted of multiagent chemotherapy and local treatment consisting of surgery (S&RT group) and/or RT (RT group). EFS and OS were analyzed with uni- and multivariable Cox regression models including known prognostic factors such as age, sex, tumor volume, surgical margins, and histologic response. S&RT was performed in 332 patients (62.9%), and 145 patients (27.5%) received definitive RT. Standard dose ≤ 53 Gy (d1) was admitted in 57.8%, high dose of 54 to 58 Gy (d2) in 35.5%, and very high dose ≥ 59 Gy (d3) in 6.6% of patients. In the RT group, RT dose was d1 in 11.7%, d2 in 44.1%, and d3 in 44.1% of patients. Three-year EFS in the S&RT group was 76.6% for d1, 73.7% for d2, and 68.2% for d3 (P=.42) and in the RT group 52.9%, 62.5%, and 70.3% (P=.63), respectively. Multivariable Cox regression revealed age ≥ 15 years (hazard ratio [HR], 2.68; 95% confidence interval [CI], 1.63-4.38) and nonradical margins (HR, 1.76; 95% CI, 1.05-2.93) for the S&RT group (sex, P=.96; histologic response, P=.07; tumor volume, P=.50; dose, P=.10) and large tumor volume (HR, 2.20; 95% CI, 1.21-4.0) for the RT group as independent factors (dose, P=.15; age, P=.08; sex, P=.40). In the combined local therapy modality group, treatment with higher RT dose had an effect on EFS, whereas higher dose of radiation when treated with definitive RT was associated with an increased OS. Indications for selection biases for dosage were found. Upcoming trials will assess the value of different RT doses in a randomized manner to control for potential selection bias.

SO-16 Proton beam radiotherapy as a valid curative local alternative modality in newly diagnosed hepatocellular carcinoma: Comparative study with radiofrequency ablation

SO-16 Proton beam radiotherapy as a valid curative local alternative modality in newly diagnosed hepatocellular carcinoma: Comparative study with radiofrequency ablation

18F-fluorocholine PET/MRI versus ultrasound and sestamibi for the localization of parathyroid adenomas.

Accurate preoperative localization is imperative to facilitate a minimally invasive parathyroidectomy (MIP) in primary hyperparathyroidism (pHPT). This study aims to compare the diagnostic value of standard-of-care localization techniques (ultrasound [US] and 99mTechnetium (99mTc) -sestamibi scintigraphy) to [F-18]-fluorocholine positron emission tomography/magnetic resonance imaging (FCH-PET/MRI) to determine the additional clinical usefulness of PET/MRI in a Canadian cohort. We conducted a prospective, appropriately powered, study to compare the diagnostic value of -FCH PET/MRI to that of the US and 99mTc-sestamibi scintigraphy for localization of parathyroid adenomas in a patient with pHPT. The primary outcome was the per-lesion sensitivity and positive predictive value (PPV) of FCH-PET/MRI, US, and 99mTc-sestamibi scintigraphy. Intraoperative surgeon localization, parathormone levels, and histopathological findings were used as reference standards. Forty-one patients underwent FCH-PET/MRI of which 36 patients had parathyroidectomy. In these 36 patients, 41 parathyroid lesions were histologically confirmed as adenomas or hyperplastic glands. Per-lesion sensitivity of FCH-PET/MRI was 82.9% and of US and 99mTc-sestamibi scintigraphy combined at 50.0%, respectively. The sensitivity of FCH-PET/MRI was superior to that of US and 99mTc-sestamibi scintigraphy (p = 0.002). In the 19 patients in whom both US and 99mTc-sestamibi scintigraphy were negative, PET/MRI correctly identified the parathyroid adenoma in 13 patients (68%). FCH-PET/MRI is a highly accurate imaging modality for localization of parathyroid adenomas in a tertiary center in North America. It is a superior functional imaging modality to 99mTc-sestamibi scintigraphy alone and more sensitive for localization of parathyroid lesions than US and 99mTc-sestamibi scintigraphy combined. This imaging modality could become the most valuable preoperative localization study given its superior performance in localizing parathyroid adenomas.

Management and outcomes of chest wall rhabdomyosarcoma: A report from the Children's Oncology Group Soft Tissue Sarcoma Committee.

Rhabdomyosarcoma (RMS) of the chest wall presents unique management challenges and local control considerations. The benefit of complete excision is uncertain and must be weighed against potential surgical morbidity. Our aim was to assess factors, including local control modality, associated with clinical outcomes in children with chest wall RMS. Forty-four children with RMS of the chest wall from low-, intermediate-, and high-risk Children's Oncology Group studies were reviewed. Predictors of local failure-free survival (FFS), event-free survival (EFS), and overall survival (OS) were assessed, including clinical characteristics and staging, primary tumor anatomic locations, and local control modalities. Survival was assessed by Kaplan-Meier analysis and the log-rank test. Tumors were localized in 25 (57%) and metastatic in 19 (43%), and they involved the intercostal region (52%) or superficial muscle alone (36%). Clinical group was I (18%), II (14%), III (25%), and IV (43%), and ultimately 19 (43%) patients had surgical resection (upfront or delayed), including 10 R0 resections. Five-year local FFS, EFS, and OS were 72.1%, 49.3%, and 58.5%, respectively. Univariate factors associated with local FFS included age, International Rhabdomyosarcoma Study (IRS) group, extent of surgical excision, tumor size, superficial tumor location, and presence of regional or metastatic disease. Other than tumor size, the same factors were associated with EFS and OS. Chest wall RMS has variable presentation and outcome. Local control is a significant contributor to EFS and OS. Complete surgical excision, whether upfront or after induction chemotherapy, is usually only possible for smaller tumors confined to the superficial musculature but is associated with improved outcomes. While overall outcomes remain poor for patients with initially metastatic tumors, regardless of local control modality, complete excision may be beneficial for patients with localized tumors if it can be achieved without excess morbidity.

Evaluation of Surgeon-Performed Ultrasonography With or Without Contrast Enhancement vs Scintigraphy in Patients With Primary Hyperparathyroidism

Scintigraphy and ultrasonography are common imaging modalities for the preoperative localization of enlarged parathyroid glands in primary hyperparathyroidism. When comparing the 2 modalities, the benefits of ultrasonography in terms of convenience, patient comfort, duration, cost, and lack of radiation should be taken into account. To investigate whether surgeon-performed ultrasonography, with or without contrast-enhanced ultrasonography (CEUS), is noninferior to scintigraphy for localizing pathological parathyroid glands in patients with primary hyperparathyroidism. Prospective, paired, noninferiority cohort study performed at a high-volume tertiary referral center for parathyroidectomy with blinded examiners and a 6-month follow-up. Participants were adults (age ≥18 years) referred for parathyroidectomy due to primary hyperparathyroidism. Of 207 eligible patients, 35 were excluded, leaving 172 enrolled in the study. Inclusion lasted from September 2019 until February 2021. Follow-up ended in December 2021. 99mTechnetium-pertechnetate/99mtechnetium-sestamibi subtraction scintigraphy with 99mtechnetium-sestamibi single-photon emission computed tomography/computed tomography, followed by surgeon-performed ultrasonography and CEUS. The sensitivity of each imaging modality in localizing pathological parathyroid glands, calculated on a per-quadrant and a per-patient basis, respectively. The a priori noninferiority margin was a lower 95% confidence limit for the difference in sensitivity not falling below -10%. Out of 172 participants, 139 (80.8%) were women, the median (range) age was 65 (24-87) years, and the median (IQR) follow-up was 200.5 (181-280.25) days. Quadrant sensitivity (95% CI) was 70.9% (63.2%-78.5%) for ultrasonography, 68.4% (60.4%-76.5%) for ultrasonography plus CEUS, and 67.0% (60.0%-74.0%) for scintigraphy. The sensitivity difference (95% CI) compared with scintigraphy was 3.9% (-4.1% to 11.8%) for ultrasonography and 1.5% (-6.4% to 9.3%) for ultrasonography plus CEUS, establishing noninferiority for both modalities. Per-patient sensitivity was 81.4% (74.8%-86.9%) for ultrasonography and 79.1% (72.2%-84.9%) for both scintigraphy and ultrasonography plus CEUS. The sensitivity difference compared with scintigraphy was 2.3% (-6.8% to 11.4%) for ultrasonography and 0.0% (-9.1% to 9.1%) for ultrasonography plus CEUS, establishing noninferiority for both modalities. In this cohort study, conventional ultrasonography by an experienced parathyroid surgeon-sonographer was noninferior to scintigraphy and may constitute a valid first-line imaging modality in patients with primary hyperparathyroidism, even without the addition of CEUS. Further imaging should be reserved for cases that are equivocal or nonlocalizing on ultrasonography.

Abstract 820: Photo-activatable ON-OFF microparticles for on-demand pulsatile drug delivery in a breast cancer model

Abstract The ability to treat tumors with high efficacy in a local microenvironment, while mitigating the side effects of systemic toxicity is an area of active investigation. Towards this goal, designing a minimally-invasive local therapeutic modality, with a controlled, pulsatile drug release mechanism is an attractive proposition. In this study, a near-infrared (NIR) photo-activatable microparticle was developed for localized, pulsatile delivery of encapsulated anticancer drugs into the tumor with simultaneous thermal ablation, with controlled ON-OFF thermal cycles using NIR laser irradiation. The microparticles were fabricated using a poly(caprolactone) (PCL) matrix, containing 2D molybdenum disulfide (MoS2) nanosheets as the NIR-responsive photothermal agent, and doxorubicin or violacein, as hydrophilic and hydrophobic model anticancer drugs, respectively. Cubic microparticles of 200 µm size were fabricated by casting a polymer-MoS2-drug film on PDMS mold with loading efficiency of 2 μg MoS2 per particle, and 0.2-8 μg of drug per particle. A cytotoxicity assay was performed to test the efficacy of the loaded microparticles in reducing the viability of 4T1 murine-derived cell culture, using the ON-OFF laser switch mechanism. In order to select a suitable laser power and duration of treatment for in vivo studies, a Machine Learning algorithm based on a Random Forest classifier was trained, to arrive at the optimal treatment conditions: 0.4-0.5 W/cm2 of laser power at 808 nm, for 3 cumulative minutes of laser irradiation, to reach the target temperature of 50 °C, which activates PCL melting and subsequent drug release. The effect of pulsatile treatment was studied in vivo in a murine-derived 4T1 subcutaneous mouse model of breast cancer, using this photo-activatable ON-OFF switch mechanism, for up to 3 cycles of laser irradiation. As control groups, tumor only (no treatment), laser only (no drug or microparticle), drug only (no laser or microparticle), microparticles only (no drug or laser), and microparticles with laser (no drug) were studied. The cohorts receiving the photo-activated 3-cyclic treatment for both drugs showed increased median survival up to 40 days post tumor induction, compared to a median survival of 16 days for the control groups. Although one laser cycle was enough to trigger drug release, there was a significant shrinkage in the tumor volume noticed with 3 cycles, with eventual scarring and shedding of the tissue with no evidence of residual tumor at the primary site. While this cyclic drug release modality is very effective at treating the primary site, subsequent histopathology revealed that the aggressive tumor in some animals had metastasized to the liver and other organs. More work is ongoing to design better targeted approaches to deliver the drug-loaded microparticles to the site of metastatic tumors, to increase the survival prospects of this disease. Citation Format: Maria Kanelli, Neelkanth M. Bardhan, Morteza Sarmadi, Shahad Alsaiari, William Rothwell, Apurva Pardeshi, Angela M. Belcher, Ana Jaklenec, Robert S. Langer. Photo-activatable ON-OFF microparticles for on-demand pulsatile drug delivery in a breast cancer model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 820.

Imaging Recommendations for Diagnosis, Staging, and Management of Cancer of the Thyroid, Parathyroid, and Salivary Glands

AbstractThyroid cancer ranks as the leading endocrine malignancy in adults. The foundation for primary diagnosis of thyroid cancer is a high-resolution ultrasound (US) of the thyroid gland including US-guided fine-needle biopsy (FNB) of suspected thyroid nodules. Advanced cross-sectional imaging, including computed tomography (CT), magnetic resonance imaging, and positron emission tomography, can be useful in selected patients. The mainstay of treatment of thyroid cancer is surgery. It may be supplemented by radioactive iodine ablation/therapy in high-risk differentiated thyroid cancer. Radiology plays a crucial role in both diagnostic and posttreatment follow-up imaging. Primary hyperparathyroidism (PHPT) is the third most common endocrine disorder with single parathyroid adenoma being its most common cause. The radiologist's aim in parathyroid imaging is to provide the clinician with an illustrative picture of the neck, locating lesions with respect to landmarks. Imaging helps in the detection of solitary versus multiglandular disease, ectopic and supernumerary glands with precise localization. US, nuclear imaging, and four-dimensional CT are the most commonly used imaging modalities for the preoperative localization of the parathyroid disease. Salivary gland tumors account for approximately 0.5% of all neoplasms, the most common location being the parotid gland (70%). Imaging is crucial in salivary gland tumors by defining its location, detecting malignant features, assessing local extension and invasion, staging the tumors according to the tumor-node-metastasis classification, and assessing the feasibility of surgery.

The role of magnetic resonance imaging and computed tomography in oral squamous cell carcinoma patients' preoperative staging.

The aim of the study was to evaluate the accuracy of MRI and CT with regard to the detection of lymph node metastases based on the data of specific patients with OSCC who received bilateral neck dissection. In a retrospective analysis from 01/2014 to 12/2020 patients who underwent primary tumor resection and bilateral neck dissection were evaluated. 174 preoperative MRI (78.74%, N=137) and CT (21.26%, N=37) were correlated with the histopathological findings. CT had a sensitivity of 67% and specificity of 68% (p=0.76). MRI showed an overall sensitivity of 66% and a specificity of 68% (p=0.76). In 52.87% of all cases no differences between cN and pN were found. MRI is the method to overestimate lymph node involvement compared to CT (overestimation in 27% vs. 21.62%). The current data indicate that MR and CT show poor efficacy in the detection of cervical metastases. Accordingly, attention must be paid to alternatives to correct local staging modalities. The application of structured bilateral neck dissection needs to be questioned.

Keratitis-ichthyosis-deafness Syndrome with Heterozygous p.D50N in the GJB2 Gene in Two Serbian Adult Patients.

Keratitis-ichthyosis-deafness (KID) syndrome is a rare congenital ectodermal dysplastic syndrome presenting with keratitis, ichthyosis and sensorineural hearing loss. The most common causes of KID syndrome are heterozygous missense mutations in the GJB2 gene that codes for connexin 26. During the ophthalmological examination, two adult females complained of recent worsening of visual acuity in both eyes. Anamnesis revealed that their eyes were red and irritated from early childhood onwards. Both of them had thickening and keratinisation of eyelid margins, lash loss, diffuse opacification of cornea and conjunctiva caused by keratinisation of eye surface, superficial and deep corneal vascularisation and corneal oedema. Partial sensorineural hearing loss and difficulties in speech were also noted along with typical ichthyosiform erythroderma. Genetic testing of the GJB2 gene revealed a heterozygous p.D50N mutation in both patients.Patients were treated with a combined topical corticosteroid and artificial tears therapy, with steroid therapy being intensified during the last month. The therapy increased the visual acuity by decreasing corneal oedema and by forming a more regular air-tear interface during the six months follow up. Subsequently, the disease progressed despite the continuation of the therapy. This is the first report of Serbian patients with KID syndrome. Despite the administration of the combined topical corticosteroid and artificial tears therapy the disease is relentlessly progressive and therapeutic success of ophthalmological signs with local therapeutic modalities used so far had been disappointing.

Radiotherapy, photodynamic therapy, and cryoablation-induced abscopal effect: Challenges and future prospects.

Local therapy modalities such as radiation therapy, photodynamic therapy, photothermal therapy, and cryoablation have been used to treat localized tumors for decades. The discovery of the abscopal effect causes a paradigm shift where local therapy also causes systemic effects and leads to the remission of nonirradiated tumors. The abscopal effect of radiation therapy, alone or in combination with other treatments, has been extensively studied over the last six decades. However, the results are unsatisfactory in producing robust, reproducible, and long-lasting systemic effects. Although immunotherapy and radiation therapy are promising in producing the abscopal effect, the abscopal effect's mechanism is still unclear, owing to various factors such as irradiation type and dose and cancer type. This article reviews the research progress, clinical and preclinical evidence of the abscopal effect by various local therapies alone and in combination with chemotherapy and immunotherapy, case reports, and the current challenges in producing the abscopal effect by various local therapies, focusing on radiotherapy, photodynamic therapy, cryoablation, and the prospects for obtaining a robust, reproducible, and long-lasting abscopal effect.

Which is better, fluoroscopic-guided or ultrasonic-guided shock wave lithotripsy for pediatric renal stones? Prospective randomized comparative study.

To compare the efficacy and clinical outcomes of two different stone localization modalities (fluoroscopic or ultrasonic) in SWL treatment of pediatric renal stones. This study was conducted in the period between January 2021 and June 2022 and included 100 children aged 2-16years who presented with radio-opaque renal pelvic stones < 20mm. The children were divided in two groups: group I, US-guided (50 patients), and group II, FS-guided SWL (50 patients). SWL was applied under general anesthesia. The follow-up of the patients included a visit every two weeks up to three months. Even though group II's stone-free rate after one month of follow-up was higher than group I's (90% vs. 84%), no statistically significant difference was found between the groups (p = 0.749). While the success rate was higher in group II than in group I (92% vs. 86%), no statistically significant difference was observed between the two groups (p = 0.338). The complication rate was 28% (14 patients) and 12% (6 patients) in Groups I and II, respectively. However, no significant difference was found between the two groups (p = 0.132). SWL is a non-invasive and safe method for treating pediatric renal stones. We recommend the use of the ultrasonic focusing modality in SWL of the pediatric age group, which has similar success rates, avoiding radiation and low complication rate instead of the fluoroscopic focusing modality, which uses ionizing radiation during SWL.

Translational albumin nanocarrier caging photosensitizer for efficient cancer photodynamic therapy.

It still remains a great challenge to efficiently treat malignant cancers which severely threaten human health. Photodynamic therapy (PDT) as a localized therapeutic modality has improved the therapeutic efficacy via chemical damage through reactive oxygen species (ROS). However, their efficacy is severely hampered by insufficient targeted delivery of photosensitizers owing to the lack of suitable carrier with facile preparation process and the clinical applicability. Herein, we applied clinically approved human serum albumin as the nanoreactor to encapsulate photosensitizers Chlorin e6 (Ce6) for enhancing their tumor accumulation and subsequently potent PDT effect against bladder cancer models. Albumin-loaded Chlorin e6 nanoparticles (CA-NPs) with rational nanoscale size exhibit increased reactive oxygen species production and excellent resistance to photobleaching. Moreover, CA-NPs could be efficiently internalized by tumor cells and locate in the lysosome, while they rapidly translocate to cytosol after irradiation to induce remarkable cytotoxicity (IC50 ∼5.8μg/ml). Furthermore, CA-NPs accumulate effectively in tumor tissue to afford total eradication of murine bladder tumor after single injection. More importantly, we also evidence the superior PDT effect in fresh human bladder tumor tissues via abundant reactive oxygen species generation and subsequent cell apoptosis. These findings demonstrate that human serum albumin acts as a universal tool to load small organic photoactivatable molecule with remarkable effectiveness and readiness for clinical translation.

Histopathologic features and parameters predicting recurrence potential of small renal masses

Abstract Background Small renal masses (SRMs) are defined as contrast-enhanced masses with a diameter of ≤4 cm, usually consistent with clinical stage T1a renal cell carcinoma (RCC). This study aimed to explore the histopathological features of a contemporary series of SRMs and investigate parameters that could predict their pathological nature, metastatic potential, and recurrence potential. Materials and methods Small renal masses were identified in 166 of 427 patients who underwent surgery for suspected RCC. The radical nephrectomy/partial nephrectomy ratio was 1:44, and autotransplantation was performed in a single case. Variables associated with metastatic recurrence of SRM were analyzed using χ2 and logistic regression models. Results Renal cell carcinoma was confirmed in 86% (n = 143) of cases, whereas benign tumors were present in 14% (n = 23) of cases. Seventeen percent of the RCC cases were high-grade (Fuhrman G3–4). Among SRMs with a diameter of &gt;2 cm, 71% were malignant. The mean ± standard deviation diameter of the removed SRMs was 28 ± 12 mm, significantly higher in the malignant SRMs group (31 ± 8 vs. 24 ± 9 mm) (p = 0.005). During follow-up, local recurrence was identified in 4 patients versus new distant metastasis in 11 patients. Metastatic lesions were detected in the lungs (1.8%), bone (1.2%), distant (1.9%) and regional lymph nodes (1.2%), liver (0.6%), and multiple organs (2.4%). Patients with malignant SRMs were significantly older than those with benign tumors (p = 0.036). The multivariate analysis identified tumor size, Fuhrman grade, stage, nodal and distant metastasis status, tumor localization, and treatment modality as characteristics significant for tumor recurrence. Conclusions The majority of treated neoplasms were malignant, but their incidence was low among SRMs with a diameter of &lt;2 cm. Our results emphasized the importance of histopathological features and treatment modalities in predicting malignant recurrence.

EARLY DETECTION AND VALIDATION OF PREVENTIVE MEASURES OF ORAL SUBMUCOSAL FIBROSIS WITH SPECIAL REFERENCE TO SARVASARA MUKHAROGA: A LITERARY REVIEW

The oral cavity is considered a reflection of the body's internal systems. As a result, significant efforts must be done to keep it healthy and free of chronic illnesses that may result in unfavourable outcomes. Oral Submucous Fibrosis (OSMF) is a chronic debilitating condition of the oral cavity that involves the formation of constricting bands of collagen fibre in the oral mucosa over time, resulting in restricted movement of the mouth and tongue and eventually hindered or problematic speech and difficulty swallowing food. Many pharmacological and surgical techniques have been used in modern terms, but the outcomes have been unsatisfactory due to recurrence and dire consequences. When the symptomatology of OSMF is compared to Ayurvedic classics, it can be classified as Vata Pitta Pradhana Sarvasara Mukharoga. An attempt was made here to explore preventive measures for OSMF using Ayurvedic methods. This study will discuss treatment at both the local and systemic levels. Local modalities such as vrana shodhana and, vrana ropana pratisarana (rubbing) &amp; kavala (gargling) halt disease progression, and these local therapies prevent and reverse fibrosis while also improving motor functions of the mouth. Systemic therapy restores balance and improves the oral mucosa's vitality. This study emphasizes how the treatment approach is superior to all other surgical and nonsurgical treatments. Early withdrawal of destructive behaviours and adequate therapy with ayurvedic medications aid in managing OSMF.

ROLE OF IMAGING IN EVALUATION OF SALIVARY GLAND TUMORS

Salivary gland tumours are a common clinical dilemma and imaging plays a useful role in establishing diagnosis, differentiating benign from malignant tumors, evaluating extent of local and distant involvement and thus providing a rm aid to the clinician for the management of these tumors. Ultrasonography is the rst line imaging modality for localization and characterization of lesions in the major salivary glands. CT /MRI help to identify spread of tumor in inaccessible areas like para-pharyngeal spaces , dene the tumor's size and extent better and give more detailed information about the involvement of surrounding structures.

Intelligent indoor metasurface robotics.

Intelligent indoor robotics is expected to rapidly gain importance in crucial areas of our modern society such as at-home health care and factories. Yet, existing mobile robots are limited in their ability to perceive and respond to dynamically evolving complex indoor environments because of their inherently limited sensing and computing resources that are, moreover, traded off against their cruise time and payload. To address these formidable challenges, here we propose intelligent indoor metasurface robotics (I2MR), where all sensing and computing are relegated to a centralized robotic brain endowed with microwave perception; and I2MR's limbs (motorized vehicles, airborne drones, etc.) merely execute the wirelessly received instructions from the brain. The key aspect of our concept is the centralized use of a computation-enabled programmable metasurface that can flexibly mold microwave propagation in the indoor wireless environment, including a sensing and localization modality based on configurational diversity and a communication modality to establish a preferential high-capacity wireless link between the I2MR's brain and limbs. The metasurface-enhanced microwave perception is capable of realizing low-latency and high-resolution three-dimensional imaging of humans, even around corners and behind thick concrete walls, which is the basis for action decisions of the I2MR's brain. I2MR is thus endowed with real-time and full-context awareness of its operating indoor environment. We implement, experimentally, a proof-of-principle demonstration at ∼2.4GHz, in which I2MR provides health-care assistance to a human inhabitant. The presented strategy opens a new avenue for the conception of smart and wirelessly networked indoor robotics.

What's New in Musculoskeletal Tumor Surgery.

What's New in Musculoskeletal Tumor Surgery.

Analysis of Local Control Outcomes and Clinical Prognostic Factors in Localized Pelvic Ewing Sarcoma Patients Treated with Radiation Therapy: A Report from the Children's Oncology Group

<h3>Purpose/Objective(s)</h3> To identify potential clinical prognostic factors associated with a higher risk of local recurrence in localized pelvic Ewing Sarcoma (ES) patients treated with radiation therapy. <h3>Materials/Methods</h3> Data for 101 patients treated with definitive radiotherapy (RT) or both surgery and radiation (S+RT) on INT-0091, INT-0154, and AEWS0031 were analyzed. Radiation and imaging data was reviewed at IROC QARC. Imaging data for patients who did not receive radiation was not available, so surgery only patients were excluded. Tumor size was classified as </≥ 8 cm in maximum dimension and </≥ 200 mL volumetrically. Pelvic subsites were categorized as sacrum, iliac/buttock, or ischiopubic-acetabulum. Five-year cumulative incidence of local failure was defined as standard. <h3>Results</h3> The most common primary pelvic subsite was sacrum, 44.6%. Median tumor size at diagnosis was 9.7 cm (range: 2.4-16.0 cm) in maximum dimension and 215.9 mL (range: 3.7-1400.0 mL) volumetrically. RT was utilized in 68% of patients and S+RT in 32%. There was no statistically significant difference in local therapy modality employed based on tumor subsite or size. The five-year cumulative incidence of local failure for the entire cohort was 19.0% (95% CI, 12.7-28.5%). RT was associated with a higher incidence of local failure at 25.0% compared to 6.3% for S+RT (p=0.046). There was no difference in local failure outcomes by tumor size </≥ 8 cm in maximum dimension or </≥ 200 mL volumetrically. A higher incidence of local failure was seen with each additional 100 mL of tumor at diagnosis for all patients (p=0.04) and for RT only patients (p=0.005). Tumors originating in the ischiopubic-acetabular region were associated with the highest local failure incidence of 37.5%, compared to 20.0% for iliac-buttock and 11.4% for sacrum (p=0.02). Ischiopubic-acetabulum tumors treated with RT alone had the highest local failure rate in the cohort (50.0%, p=0.06). Multivariable analysis demonstrated RT alone (HR 5.1, p=0.04), tumor subsite (particularly ischiopubic-acetabulum tumors, HR 4.6, p=0.02), and increasing volume per 100 mL (HR 1.2, p=0.01) were associated with a higher incidence of local recurrence. <h3>Conclusion</h3> Patients with pelvic ES selected for S+RT had lower rates of local failure compared to patients selected for definitive RT. Tumors involving the ischiopubic-acetabular region and increasing tumor volume at diagnosis likely correlate with inferior local tumor control outcomes, especially for RT only patients, indicating local therapy intensification may be warranted for this cohort. Tumor characteristics did not correlate with choice of local therapy modality suggesting an opportunity to develop best local therapy practices guidelines for future studies based on tumor features.