Postoperative Cavity Research Articles

Engineering Cells for Cancer Therapy.

ConspectusCells, particularly living cells, serve as natural carriers of bioactive substances. Their inherent low immunogenicity and multifunctionality have garnered significant attention in the realm of disease treatment applications, specifically within the domains of cancer immunotherapy and regenerative tissue repair. Nevertheless, several prominent challenges impede their swift translation into clinical applications, including obstacles related to large-scale production feasibility and high utilization costs. To address these issues comprehensively, researchers have proposed the notion of bionic cells that are synthetically generated through chemical or biosynthetic means to emulate cellular functions and behaviors. However, artificial cell strategies encounter difficulties in fully replicating the intricate functionalities exhibited by living cells while also grappling with the complexities associated with design implementation for clinical translation purposes. The convergence of disciplines has facilitated the reform of living cells through a range of approaches, including chemical-, biological-, genetic-, and materials-based methods. These techniques can be employed to impart specific functions to cells or enhance the efficacy of therapy. For example, cells are engineered through gene transduction, surface modifications, endocytosis of drugs as delivery systems, and membrane fusion. The concept of engineered cells presents a promising avenue for enhancing control over living cells, thereby enhancing therapeutic efficacy while concurrently mitigating toxic side effects and ultimately facilitating the realization of precision medicine.In this Account, we present a comprehensive overview of our recent research advancements in the field of engineered cells. Our work involves the application of biological or chemical engineering techniques to manipulate endogenous cells for therapeutics or drug delivery purposes. For instance, to avoid the laborious process of isolating, modifying, and expanding engineered cells in vitro, we proposed the concept of in situ engineered cells. By applying a hydrogel loaded with nanoparticles carrying edited chimeric antigen receptor (CAR) plasmids within the postoperative cavity of glioma, we successfully targeted tumor-associated macrophages for gene editing, leading to effective tumor recurrence inhibition. Furthermore, leveraging platelet's ability to release microparticles upon activation at injury sites, we modified antiprogrammed death 1 (PD-1) antibodies on their surface to suppress postoperative tumor recurrence and provide immunotherapy for inoperable tumors. Similarly, by exploiting bacteria's active tropism toward sites of inflammation and hypoxia, we delivered protein drugs by engineered bacteria to induce cancer cell death through pyroptosis initiation and immunotherapy strategies. In the final section, we summarize our aforementioned research progress while providing an outlook on cancer therapy and the hurdles for clinical translation with potential solutions or future directions based on the concept of engineered cells.

Half canal wall down tympanomastoidectomy.

The purpose of this study is to analyse the effect of half canal wall down tympanomastoidectomy in the treatment of chronic otitis media or cholesteatoma. In this retrospective study, the half canal wall down tympanomastoidectomy technique was used at our hospital for chronic otitis media or cholesteatoma removal in 265 adult patients, representing 271 operated ears, with an average follow-up time of 8.4 years. The post-operative cavities were slightly wider and straighter in 91.9 per cent of the ears. Fifteen per cent of the patients needed cavity cleaning every six months, 25 per cent of them needed cavity cleaning every year and 60 per cent of the patients had a self-cleaning cavity. Only one patient with a cleft palate experienced cholesteatoma recurrence in the mesotympanum. The half canal wall down tympanomastoidectomy technique showed a low-recurrence rate and satisfying operative cavities. The half canal wall down tympanomastoidectomy technique is a good choice for middle ear surgery.

Fractionated stereotactic radiotherapy of intracranial postoperative cavities after resection of brain metastases – Clinical outcome and prognostic factors

Background and PurposeAfter surgical resection of brain metastases (BM), radiotherapy (RT) is indicated. Postoperative stereotactic radiosurgery (SRS) reduces the risk of local progression and neurocognitive decline compared to whole brain radiotherapy (WBRT). Aside from the optimal dose and fractionation, little is known about the combination of systemic therapy and postoperative fractionated stereotactic radiotherapy (fSRT), especially regarding tumour control and toxicity. MethodsIn this study, 105 patients receiving postoperative fSRT with 35 Gy in 7 fractions performed with Cyberknife were retrospectively reviewed. Overall survival (OS), local control (LC) and total intracranial brain control (TIBC) were analysed via Kaplan-Meier method. Cox proportional hazards models were used to identify prognostic factors. ResultsMedian follow-up was 20.8 months. One-year TIBC was 61.6% and one-year LC was 98.6%. Median OS was 28.7 (95%-CI: 16.9–40.5) months. In total, local progression (median time not reached) occurred in 2.0% and in 20.4% radiation-induced contrast enhancements (RICE) of the cavity (after median of 14.3 months) were diagnosed. Absence of extracranial metastases was identified as an independent prognostic factor for superior OS (p = <0.001) in multivariate analyses, while a higher Karnofsky performance score (KPS) was predictive for longer OS in univariate analysis (p = 0.041). Leptomeningeal disease (LMD) developed in 13% of patients. ConclusionFSRT after surgical resection of BM is an effective and safe treatment approach with excellent local control and acceptable toxicity. Further prospective randomized trials are needed to establish standardized therapeutic guidelines.

In English

Artificial implants are a favorable environment for bacterial adhesion and subsequent biofilm formation, thereby accelerating the development of infection in the area of implant incorporation. Despite significant progress in the development of various endoprostheses over the past decades, bacterial periprosthetic infection is one of the main factors leading to complications in their use, prolongation of rehabilitation, and significant economic losses. The present work is devoted to the creation of hybrid hydrogel nanocomposites with complex antimicrobial action for endoprosthetics in the maxillofacial region and for filling postoperative cavities (primarily after tumor removal). These nanocomposites were created on the basis of pre-synthesized spongy polyvinylformal with encapsulated gold nanoparticles, the pore space of which was partially filled with pH-sensitive hydrogels based on acrylic acid (or copolymers based on acrylamide and acrylic acid) with sorbed Albucid. The structure of the synthesized hybrid hydrogel materials was confirmed by IR spectroscopy. Studies of the kinetics of hydrogel swelling in buffer solutions with different pH values have shown that the sample filled with a copolymer of acrylamide and acrylic acid with their ratio 95:5 has the optimal properties for preserving the geometric dimensions of the material for endoprosthetics, while in the case of incorporation of 100 % acrylic acid, the degree of swelling of the material (and, respectively, its dimensions) can vary significantly with a change of рН. Antimicrobial effect of the developed hybrid hydrogel materials was investigated using the following bacterial cultures: Escherichia coli ATCC 25922, Enterococcus faecalis ATCC 29213, Staphylococcus aureus ATCC 25923, and Pseudomonas aeruginosa ATCC 27853. The antibacterial effect of polyvinylformal-based composites with incorporated gold nanoparticles that were saturated with Albucid on all test microorganisms was demonstrated (growth inhibition zones ranged from 15 to 35 mm), which will prevent microbial contamination of the developed hybrid hydrogel material when it is used in endoprosthesis.

Hypofractionated Stereotactic Radiosurgery in the Management of Brain Metastases.

Stereotactic radiosurgery (SRS) is an important weapon in the management of brain metastases. Single-fraction SRS is associated with local control rates ranging from approximately 70% to 100%, which are largely dependent on lesion and postoperative cavity size. The rates of local control and improved neurocognitive outcomes compared with conventional whole-brain radiation therapy have led to increased adoption of SRS in these settings. However, when treating larger targets and/or targets located in eloquent locations, the risk of normal tissue toxicity and adverse radiation effects within healthy brain tissue becomes significantly higher. Thus, hypofractionated SRS has become a widely adopted approach, which allows for the delivery of ablative doses of radiation while also minimizing the risk of toxicity. This approach has been studied in multiple retrospective reports in both the postoperative and intact settings. While there are no reported randomized data to date, there are trials underway evaluating this paradigm. In this article, we review the role of hypofractionated SRS in the management of brain metastases and emerging data that will serve to validate this treatment approach. Pertinent articles and references were obtained from a comprehensive search of PubMed/MEDLINE and clinicaltrials.gov .

CTNI-14. NEOADJUVANT STEREOTACTIC RADIOSURGERY (NASRS) FOR LARGE BRAIN METASTASES (BRM): RESULTS OF AN INTERNATIONAL MULTICENTER PHASE II TRIAL

Abstract BACKGROUND We conducted an international multi-center phase II trial evaluating NASRS for BrM. We hypothesized that radiation necrosis (RN) would be lower than post-operative cavity radiotherapy since the tissues receiving the highest radiation dose are resected in NASRS. METHODS BrM patients with 1 index lesion ( &amp;gt;2 and &amp;lt;5 cm in greatest diameter) suitable for resection, and 9 or less additional BrM (&amp;lt; 3 cm in greatest diameter, not requiring resection) were recruited across 3 centres. SRS was administered a median 3 (range: 2-21) days prior to surgical resection. A single fraction of 15-21 Gy was delivered, targeting the index tumor with a 2mm margin. From a sample of 30 patients, the primary endpoint was the 1-year rate of grade 2+ (G2+) RN from the index lesion. Secondary endpoints included local failure (LF), leptomeningeal disease (LMD) and overall survival (OS). RESULTS We enrolled 35 patients [Mean age (SD): 58.9 (12.9) years, 46% female] between 2018 and 2022. The most common primary histologies were lung (40%), and gastrointestinal (20%) cancers. The median BrM volume prior to surgery was 16.6 cc (range 3.2 -38.0); median index lesion size was 3.2 (range: 1.9-4.5) cm. All participants received planned protocol treatment; n = 30 are currently available for 1 year outcomes. No patients developed G2+ RN; 5 had a LF (1-year rate 38%) at 5-12-months following surgery, all of whom had an en-bloc resection. One patient each developed classic LMD and pachymeningeal failure 3 and 11 months after surgery, respectively. Median OS was 11.5 months. CONCLUSION No patients in our study experienced G2+ RN. The 1-year rate of LF was higher than anticipated, indicating the potential benefit of considering a higher radiation dose or larger margins for improved outcomes.

RADT-09. CLINICAL OUTCOMES OF FRACTIONATED STEREOTACTIC RADIOTHERAPY FOR INTACT AND POSTOPERATIVE RADIORESISTANT RENAL CELL CARCINOMA AND MELANOMA BRAIN METASTASES

Abstract PURPOSE Fractionated Stereotactic Radiotherapy (FSRT) may be an optimal strategy for radioresistant renal cell carcinoma (RCC) and melanoma brain metastases (BM). We reviewed our institutional experience of FSRT to intact BM and postoperative cavities for patients with melanoma and RCC. METHODS We retrospectively identified consecutive patients with melanoma and renal cell carcinoma with unresected or resected BM treated with FSRT at our institution from 1/2018 to 1/2021. Time to event outcomes were estimated using the Kaplan-Meier method with log-rank tests and multivariable Cox regression analyses. RESULTS We identified 44 patients with a total of 64 BM: 31 intact (48.4%) and 33 resected BMs (51.6%). Thirty-six (81.8%) were melanoma and eight (18.2%) were RCC. The majority of intact BM (n = 22/31; 71%) and cavities (n = 21/33; 64%) were treated to 30 Gy (24-30) in 5 fractions and 25 Gy (24-35), respectively. Median PTV volume for intact BM was 5.04 cc (1.2-19.8) and for resected BM was 16.7 cc (4.8-89.1). Median interval from planning MRI to FSRT was 10 days (3-28). Median time from surgery to FSRT was 37 days (9-90). At 18.6 months median follow-up, local and intracranial distant failures were observed in 4 and 20 patients, respectively. Our cohort had a local recurrence-free survival (LRFS) of 83% and overall survival (OS) of 57% at 12 months; no difference between primary FSRT versus surgery followed by FSRT (p = 0.93 and p = 0.52, respectively). On MVA, higher FSRT dose was associated with better local control (p = 0.01). Radiation Necrosis (RN) was observed in eight treatment areas (12.5%). Neither resection status (p = 0.99) nor PTV volume (p = 0.61) were associated with RN. CONCLUSION FSRT is associated with low rates of toxicity and clinically significant disease control for both intact and resected melanoma and RCC BM, with higher FSRT dose being correlated with improved control.

A Prospective Registry Study of 68Ga-DOTATATE PET/CT Incorporation Into Treatment Planning of Intracranial Meningiomas

IntroductionThe current standard for meningioma treatment planning involves MRI-based image guidance. SSTR ligands such as 68Ga-DOTATATE are being explored for meningioma treatment planning due to near-universal expression of somatostatin receptor 1/2 in meningioma tissue. We hypothesize that 68Ga-DOTATATE PET-guided treatment management for meningioma patients will be safe, effective, and identify which patients benefit most from adjuvant radiotherapy. MethodsA single institution prospective registry study was created and included intracranial meningioma patients who received a 68Ga-DOTATATE PET scan to assist with radiation oncologist decision-making. Patients who received a PET scan from 1/1/2018-2/25/2022 were eligible for inclusion. Results60 patients were treated in this registry. 40%, 47%, and 5% of patients had WHO Grades 1, 2, and 3 meningiomas. 5 cases (8%) did not have a grade assigned. 22%, 72%, and 7% were categorized as RTOG 0539 high, intermediate, and low-risk, respectively. After completing their PET scan, 48, 11, and 1 patient(s) proceeded with RT, observation, or redo craniotomy. The median follow-up for the entire cohort was 19.5 months. 3 patients (5%) experienced local failure (LF) between 9.2-28.5 months after diagnosis. 2 patients with LF had PET-avid disease in their post-operative cavity and elected for observation prior to recurrence, and 1 high-risk patient with multifocal disease experienced LF 2 years after a second radiation course and multiple previous recurrences. Notably, 5 patients did not have any local PET uptake and were observed; none of these patients experienced recurrence. There was only one Grade 3 toxicity attributed to PET-guided radiation. ConclusionThis is one of the largest known population of intracranial meningioma patients followed by physicians who utilized 68Ga-DOTATATE PET guided therapy. Incorporating 68Ga-DOTATATE PET into future trials may assist with clinician decision-making and improve patient outcomes.

Clinical Outcomes Following Postoperative Cavity Stereotactic Radiosurgery for Brain Metastases

We evaluated outcomes of patients with brain metastases (BM) treated with surgical resection and postoperative cavity stereotactic radiosurgery (SRS) to identify which baseline characteristics and treatment factors may increase risk for local recurrence (LR). From June 2017 to December 2021, 68 patients underwent surgical resection for BM followed by single-fraction SRS (n = 15) or fractionated SRS (FSRS) in 3 (n = 24) or 5 (n = 29) fractions to the postoperative cavity using frameless LINAC-based technique. Patients treated with surgery alone or surgery with postoperative whole brain radiotherapy (WBRT) were excluded. Median prescription doses were 1600 cGy (range: 1440-1875) in 1 fraction, 2400 cGy (range: 2100-2700) in 3 fractions, and 3000 cGy (range: 2500-3000) in 5 fractions. Local control (LC) and overall survival (OS) were estimated by the Kaplan-Meier method. Cox proportional hazards models were used to compare groups. Median follow-up was 19.5 months (IQR: 9.0-34.7). Median patient age was 62.5 years (range: 24-80), and 38 (55.9%) patients were male. Primary tumors were lung (n = 29), including NSCLC (n = 28) and SCLC (n = 1), melanoma (n = 12), breast (n = 11), and other (n = 16). Median preoperative tumor maximal dimension was 3.5cm (range: 1.1-6.3). Median planning treatment volume (PTV) was larger in the FSRS group (26.2cc (range: 6.5-151.8)) than in the SRS group (7.7cc (range: 1.1-11.5)) (p<0.001). Median number of concurrently treated intact lesions was 0 (range: 0-13). Median time from surgery to SRS was 32 days (range: 14-77). Forty-eight (70.6%) patients were treated with immunotherapy or targeted therapy. Median OS was 22.3 months (95% CI: 14.4-30.9). The 1-year and 2-year OS rates were 70% and 48%, respectively. The 1-year and 2-year LC rates were 86% and 73%, respectively. Median time to LR was 8.4 months (95% CI: 4.4-11.0). Among the 14 patients with LR, 11 had undergone salvage therapy at last follow-up which included repeat SRS (n = 4), WBRT (n = 3), palliative local radiotherapy (n = 2), surgery followed by repeat SRS (n = 1), and systemic therapy (n = 1). Eleven (16.2%) patients ultimately underwent WBRT post-SRS for local and/or distant failure. No difference in LC was observed based on primary tumor, time interval between resection and SRS, PTV volume, prescription dose, or fractionation regimen (SRS v. FSRS). However, all LR in the 3-fraction group occurred in patients who received less than 2700 cGy. Favorable LC and OS outcomes were observed following postoperative cavity SRS for resected BM in a modern cohort with a large percentage of patients receiving immunotherapy or targeted therapy. No prognostic factors were identified for LC which may be attributable to the cohort size and small number of events observed. However, our findings suggest that patients who undergo 3-fraction FSRS should be treated to a total dose of 2700 cGy to maximize LC.

Efficacy and Toxicity of Different Target Volume Delineations of Radiotherapy Based on the Updated RTOG/NRG and EORTC Guidelines in Patients with High Grade Glioma: A Randomized, Controlled Clinical Trial

Postoperative radiotherapy with concomitant and adjuvant temozolomide (TMZ) is the standard of care for newly diagnosed high grade glioma, but the optimal method for target volume delineations for intensity modulated radiation therapy (IMRT) is still unclear. We hypothesized that compared with the EORTC guidelines, IMRT based on the updated RTOG/NRG guidelines was equally effective, without increasing toxicities for patients with high-grade glioma. The purpose of this randomized phase 2 study was to compare the efficacy and toxicity of IMRT based on different target volume delineations (updated RTOG/NRG versus EORTC guidelines) with concomitant and adjuvant TMZ for patients with high grade glioma. A total of 302 patients with newly diagnosed high-grade glioma (WHO grade 3-4) were randomly assigned (1:1) to receive postoperative IMRT based on either updated RTOG/NRG guidelines (RTOG/NRG group, n = 151) or EORTC guideline (EORTC group, n = 151), with concomitant and adjuvant TMZ. In the RTOG/NRG group, an initial volume consisting of enhancement, postoperative cavity, plus surrounding edema (or fluid-attenuated inversion recovery [FLAIR] abnormality defined by magnetic resonance imaging [MRI]) and a 2-cm margin received 46 Gy in 23 fractions followed by a boost of 14 Gy in 7 fractions to the area of enhancement plus the cavity and a 2-cm margin. In the EORTC group, a single planning volume was used to deliver 60 Gy in 30 fractions to the area of enhancement and the cavity with a 2-cm margin. The primary end point was overall survival (OS). Secondary end points included progression-free survival (PFS) and toxicities associated with each treatment. No statistically significant differences were observed between groups for 1-year OS (71.8% for RTOG/NRG group and 69.9% for EORTC group, respectively; P = 0.759) or 1-year PFS (46.7% for RTOG/NRG group and 43.6% for EORTC group, respectively; P = 0.674). Efficacy did not differ by MGMT methylation status. There were no differences in grade 3-4 toxicities (leukopenia, lymphopenia, neutropenia, thrombocytopenia, fatigue, nausea and vomiting) between the two groups. No grade 5 toxicities were observed in both groups. Multivariate analyses showed that tumor MGMT status (methylated vs unmethylated) and WHO grade (grade 3 vs grade 4) were associated with OS and PFS. However, radiation type (RTOG/NRG group vs EORTC), sex, age, and Karnofsky scale did not significantly influence OS or PFS. Compared with EORTC guidelines for postoperative radiotherapy, IMRT based on RTOG/NRG guidelines was equally effective, without increasing toxicities for patients with high-grade glioma. This trial is registered with chictr.org.cn, number ChiCTR2100046667.

Stereotactic Radiosurgery (SRS) for Large Brain Metastases: Dosimetric and Clinical Predictors of Local Progression and Radionecrosis

Stereotactic radiosurgery (SRS) provides high rates of local control for small brain metastases with low rates of radionecrosis (RN). Larger targets are associated with increased risk of both local progression (LP) and RN. In this analysis, we hypothesized that dosimetric and clinical parameters predict for risk of LP and RN in SRS targets larger than two centimeters. We retrospectively reviewed patients with one or more targets with either an intact versus post-operative cavity larger than 2.0 cm treated with LINAC-based SRS between 2017 and 2022 at one institution. We assessed for association between patient, treatment, and disease variables with LP and RN. Variables assessed included tumor resection status, PDL1 positivity, target volume, maximum and minimum target dose, EQD2 and BED (a/b = 2 for necrosis and a/b = 10 for tumor control), as well as receipt of steroids, bevacizumab, or systemic therapy before or after SRS. Radionecrosis was determined by characteristic radiographic changes. Analyses were performed for the entire cohort and within subsets including by resection status and dose fractionation. A total of 178 lesions in 143 patients were included. Targets with volume diameters measuring at least 2 cm were used. Median follow-up was 2.3 years. Overall survival at 1 and 2 years was 56% and 32%, respectively. Most lesions (n = 119) were resected and treated with SRS post-operatively. The most common dose and fractionation schemes used were 30 Gy in 5 fractions (n = 89) and 27 Gy in 3 fractions (n = 63). For the entire cohort, the cumulative incidence of LP 1 and 2 years was 26% and 34%, respectively. The cumulative incidence of radiographic radionecrosis at 1 and 2 years was 12% and 17%, respectively. There was no difference in LP or RN between 27 Gy in 3 fractions versus 30 Gy in 5 fractions (p>0.5 for both). Median planning target volume (PTV) size was 18.5 cc for the 27 Gy in 3 fraction group compared to 21.9 cc in the 30 Gy in 5 fraction group. Minimum or maximum dose within the target was not associated with increased risk of LP or RN. Among patients receiving 27 Gy in 3 fractions, patients treated with resection followed by SRS had lower risk of LP compared to those treated with SRS alone (HR: 0.15, 95% CI: 0.03-0.64, p = 0.011). Among patients receiving 30 Gy in 5 fractions, patients who received corticosteroids prior to SRS had a lower risk of RN (HR: 0.14, 95% CI: 0.03-0.66, p = 0.013). For the entire cohort as well as within all subgroups, PD-L1≥1% was associated with increased risk of RN (p<0.001 for all). Selecting the optimal SRS dose fractionation and planning parameters to minimize both LP and RN remains a challenge for large targets. In this analysis, 27 Gy in 3 fractions appeared to provide equivalent LP and RN compared to 30 Gy in 5 fractions, and may be more convenient for patients. Patients with PD-L1≥1% with large brain targets treated with SRS may be at increased risk of RN; corticosteroid prophylaxis may be considered in this population.

Impact of Concurrent Targeted Therapy and Immunotherapy on the Incidence of Radiation Necrosis Following Stereotactic Radiosurgery for Brain Metastases

The management of metastatic disease has evolved with the advent of immunotherapy (IT) and targeted therapies (TT). Yet, there is limited understanding of the toxicity associated with combining these agents with stereotactic radiosurgery (SRS). We retrospectively evaluated the impact of concurrent systemic therapy (ST) on the risk of radiation necrosis (RN) following LINAC-based SRS for brain metastases (BM). A retrospective study was conducted within an integrated health care system from March 2017 to December 2021 of 313 patients who underwent SRS or fractionated SRS in 3 or 5 treatments to a total of 1,644 intact BM. Post-operative cavity SRS and re-irradiated lesions were excluded. RN was diagnosed using perfusion MRI, contrast clearance MRI, or serial standard MRI and graded using CTCAE (v.5). Concurrent ST was defined as administration within 1 month preceding or following SRS. Overall survival (OS) and risk of RN were estimated by the Kaplan-Meier method. Logistics regression analyses were performed to compare risk of RN in patients who received concurrent systemic therapy to those who did not, adjusted for PTV volume and receipt of whole brain radiotherapy (WBRT). Median follow-up was 12.2 months. Median age was 64 years (range: 24-92). Primary sites per patient included lung (48.9%), breast (18.2%), melanoma (11.5%), kidney (6.1%), and other (15.3%). Median total lesions treated was 3 (range: 1-44); 65.9% of patients underwent 1 course of SRS, 23.4% underwent 2 courses, 6.2% underwent 3 courses, 4.5% underwent >4 courses. Seventy-six (24.2%) patients received WBRT. Overall, 70.6% of lesions received concurrent ST including chemotherapy (CT) (32.5%), IT (26.8%), and TT (27.6%); 16.4% received a combination of ST. Median OS was 12.9 months (95% CI: 10.4-15.5). RN was observed in 50 (3.0%) lesions in 42 (13.4%) patients. The 1-year risk of RN was 4.0% per lesion and 15.4% per patient. Symptomatic RN (SRN) was observed in 31 (1.9%) lesions in 24 (7.7%) patients. The 1-year risk of SRN was 2.7% per lesion and 10.1% per patient. When compared to lesions treated without concurrent systemic therapy, there was no increased risk of RN observed in lesions treated with concurrent CT (adjusted OR = 0.86 (95% CI: 0.43-1.73) p = 0.68), concurrent IT (adjusted OR = 0.84 (95% CI: 0.41-1.71) p = 0.84), or concurrent TT (adjusted OR = 0.57 (95% CI: 0.25-1.30) p = 0.18). Treatments of SRN included dexamethasone (96.8%), bevacizumab (22.6%), and laser interstitial thermal therapy (6.5%). Concurrent IT and TT appears well-tolerated in patients who undergo SRS for treatment of BM. No increased risk of RN was observed in lesions treated with concurrent IT or TT compared to lesions treated in the absence of concurrent ST. Further prospective and agent-specific evaluation is necessary to confirm these findings.

Computational mechanobiology model evaluating healing of postoperative cavities following breast-conserving surgery

Breast cancer is the most commonly diagnosed cancer type worldwide. Given high survivorship, increased focus has been placed on long-term treatment outcomes and patient quality of life. While breast-conserving surgery (BCS) is the preferred treatment strategy for early-stage breast cancer, anticipated healing and breast deformation (cosmetic) outcomes weigh heavily on surgeon and patient selection between BCS and more aggressive mastectomy procedures. Unfortunately, surgical outcomes following BCS are difficult to predict, owing to the complexity of the tissue repair process and significant patient-to-patient variability. To overcome this challenge, we developed a predictive computational mechanobiological model that simulates breast healing and deformation following BCS. The coupled biochemical-biomechanical model incorporates multi-scale cell and tissue mechanics, including collagen deposition and remodeling, collagen-dependent cell migration and contractility, and tissue plastic deformation. Available human clinical data evaluating cavity contraction and histopathological data from an experimental porcine lumpectomy study were used for model calibration. The computational model was successfully fit to data by optimizing biochemical and mechanobiological parameters through Gaussian process surrogates. The calibrated model was then applied to define key mechanobiological parameters and relationships influencing healing and breast deformation outcomes. Variability in patient characteristics including cavity-to-breast volume percentage and breast composition were further evaluated to determine effects on cavity contraction and breast cosmetic outcomes, with simulation outcomes aligning well with previously reported human studies. The proposed model has the potential to assist surgeons and their patients in developing and discussing individualized treatment plans that lead to more satisfying post-surgical outcomes and improved quality of life.

Iodide-Induced Severe Encephalopathy: A Case Report and Literature Review.

A physically independent and mentally competent 61-year-old gentleman was diagnosed with left upper alveolar spindle cell carcinoma. He underwent left infrastructure maxillectomy with reconstruction and had bismuth iodoform paraffin paste packed in the post-operative cavities. The patient subsequently exhibited labile emotions and acute delirium. Further investigation showed that his urine iodine level was highly elevated. He eventually made a full recovery and returned home.

Reduced malignant glioblastoma recurrence post-resection through the anti-CD47 antibody and Temozolomide co-embedded in-situ hydrogel system.

Infiltrative glioma growth makes surgical excision incomplete, and the residual tumor cells proliferate rapidly. Residual glioma cells evade phagocytosis by macrophages through upregulating anti-phagocytosis molecule CD47, which binds to the signal regulatory protein alpha (SIRPα) of macrophages. Specifically, blocking the CD47-SIRPα pathway is a potential strategy for post-resection glioma treatment. In addition, the anti-CD47 antibody (α-CD47) in combination with temozolomide (TMZ) caused an enhanced pro-phagocytic effect due to the TMZ not only destroying DNA but also inducing endoplasmic reticulum stress response of glioma cells. However, the obstruction of the blood-brain barrier makes systemic combination therapy not ideal for post-resection glioma treatment. Herein, we designed a temperature-sensitive hydrogel system based on a moldable thermosensitive hydroxypropyl chitin (HPCH) copolymer to encapsulate both α-CD47 and TMZ as α-CD47&TMZ@Gel for in situ postoperative cavity administration. Through the in vitro and in vivo evaluations, α-CD47&TMZ@Gel significantly inhibited glioma recurrence post-resection through enhancement of pro-phagocytosis of macrophages, recruitment, and activation of CD8+ T cells and NK cells.

Irreversible electroporation for post-operative margin therapy to prevent cancer recurrence based on triboelectric nanogenerator driven balloon catheter

Even though cancer therapeutic methods are improving rapidly, cancer recurrence has always remained a big challenge. Even a small lesion of missed neoplastic cells during the surgery can result in tumor recurrence and the consequent silent metastasis, making this issue more critical and complicated for prognosis. Hence, developing new methods with capability of clearing margins without side effects to the healthy surrounding tissues has always been a significant concern. This study introduced a method to prevent cancer recurrence by exposing cavity side margins to irreversible electroporation (IRE) through a balloon catheter. For this purpose, the induced tumor in BALB/c mice (as in-vivo animal model) is mostly resected, and just a traceable part is left as a model of the involved margin. A balloon-catheter is then filled with the conductive saline and inserted into the postoperative cavity. The IRE is applied through a low-cost high-voltage triboelectric nanogenerator (TENG) that is connected to the balloon catheter. Delivering a homogenous IRE without any muscle contraction by the elastic spherical balloon ensures that all the margin surfaces are exposed to the electric field. Monitoring the size of the remained tumor by the sonography imaging reveals that just 15 days of TENG-based balloon catheter irreversible electroporation (TBC-IRE) reduces the size of remained tumor by 94%, while 303% growth is observed in the remained tumor of control group of mice. Further histological analysis of this treatment disclosed no remarkable side effects on the adjacent tissue or organ. Everything considered, margin therapy by TBC-IRE can be a promising method for preventing cancer recurrence and potentially improving cancer-bearing patients' survival.

Minimizing Intracranial Disease Before Stereotactic Radiation in Single or Solitary Brain Metastases.

Stereotactic radiotherapy (SRT) in multiple fractions (typically ≤5) can effectively treat a wide range of brain metastases, including those less suitable for single-fraction stereotactic radiosurgery (SRS). Prior prospective studies on surgical resection with stereotactic radiation have focused exclusively on SRS, and retrospective studies have shown equivocal results regarding whether surgery is associated with improved outcomes compared with SRT alone. We compared resection with postoperative cavity SRT or SRS to SRT alone in patients with 1 brain metastasis, while including patients receiving SRS alone as an additional reference group. We studied 716 patients in a retrospective, single-institution cohort diagnosed with single or solitary brain metastases from 2007 to 2020. Patients receiving whole-brain radiotherapy were excluded. Cox proportional hazards models were constructed for overall survival and additional intracranial outcomes. After adjustment for potential confounders, surgery with cavity SRT/SRS was associated with decreased all-cause mortality (hazard ratio [HR]: 0.39, 95% CI [0.27-0.57], P = 1.52 × 10 -6 ) compared with SRT alone, along with lower risk of neurological death attributable to intracranial tumor progression (HR: 0.46, 95% CI [0.22-0.94], P = 3.32 × 10 -2 ) and radiation necrosis (HR: 0.15, 95% CI [0.06-0.36], P = 3.28 × 10 -5 ). Surgery with cavity SRS was also associated with decreased all-cause mortality (HR: 0.52, 95% CI [0.35-0.78], P = 1.46 × 10 -3 ), neurological death (HR: 0.30, 95% CI [0.10-0.88], P = 2.88 × 10 -2 ), and radiation necrosis (HR: 0.14, 95% CI [0.03-0.74], P = 2.07 × 10 -2 ) compared with SRS alone. Surgery was associated with lower risk of all-cause mortality and neurological death in cardinality-matched subsets of the cohort. Among surgical patients, gross total resection was associated with extended overall survival (HR: 0.62, 95% CI [0.40-0.98], P = 4.02 × 10 -2 ) along with lower risk of neurological death (HR: 0.31, 95% CI [0.17-0.57], P = 1.84 × 10 -4 ) and local failure (HR: 0.34, 95% CI [0.16-0.75], P = 7.08 × 10 -3 ). In patients with 1 brain metastasis, minimizing intracranial disease specifically before stereotactic radiation is associated with improved oncologic outcomes.

Hypofractionated stereotactic radiosurgery (HSRS) as a salvage treatment for brain metastases failing prior stereotactic radiosurgery (SRS)

Various treatment options exist to salvage stereotactic radiosurgery (SRS) failures for brain metastases, including repeat SRS and hypofractionated SRS (HSRS). Our objective was to report outcomes specific to salvage HSRS for brain metastases that failed prior HSRS/SRS. Patients treated with HSRS to salvage local failures (LF) following initial HSRS/SRS, between July 2010 and April 2020, were retrospectively reviewed. The primary outcomes were the rates of LF, radiation necrosis (RN), and symptomatic radiation necrosis (SRN). Univariable (UVA) and multivariable (MVA) analyses using competing risk regression were performed to identify predictive factors for each endpoint. 120 Metastases in 91 patients were identified. The median clinical follow up was 13.4 months (range 1.1-111.1), and the median interval between SRS courses was 13.1 months (range 3.0-56.5). 115 metastases were salvaged with 20-35Gy in 5 fractions and the remaining five with a total dose ranging from 20 to 24Gy in 3-fractions. 67 targets (56%) were postoperative cavities. The median re-treatment target volume and biological effective dose (BED10) was 9.5cc and 37.5Gy, respectively. The 6- and 12- month LF rates were 18.9% and 27.7%, for RN 13% and 15.6%, and for SRN were 6.1% and 7.0%, respectively. MVA identified larger re-irradiation volume (hazard ratio [HR] 1.02, p = 0.04) and shorter interval between radiosurgery courses (HR 0.93, p < 0.001) as predictors of LF. Treatment of an intact target was associated with a higher risk of RN (HR 2.29, p = 0.04). Salvage HSRS results in high local control rates and toxicity rates that compare favorably to thosesingle fraction SRS re-irradiationexperiences reported in the literature.

СОВРЕМЕННЫЕ ВОЗМОЖНОСТИ ДИАГНОСТИКИ И ЛЕЧЕНИЯ ОТОМИКОЗОВ

Оtomycosis is a fungal infection affecting the structures of the external auditory canal, middle ear, as well as the postoperative cavity of the mastoid process after mastoidotomy. Despite the rapid progress of modern medicine, the number of patients with fungal infections of the ENT organs, in particular the outer and middle ear, including the postoperative cavity of the middle ear, is growing every year. Fungi make up a vast group of lower chlorophyll-free plants. The group of fungi pathogenic for humans includes multicellular and unicellular microorganisms of various origins, different habitats and living conditions. Conditionally pathogenic fungi are widespread in the environment and constantly come into contact with the macroorganism, being commensals, the inflammatory process caused by them should be considered as a manifestation of a violation of the biological protective barriers of the body. The reasons for this are: immunodeficiency states, the use of broad-spectrum antibiotics, corticosteroids and mechanical trauma to the ear. The author analyzes the literature and statistical data about the prevalence of certain types of fungi in case of ear affection, the clinical picture depends on the pathogen, as well as what methods of treatment and diagnostics are used to treat otomycosis. Modern methods of conservative therapy have good results in the treatment of otitis externa. However, there are very few data on the topic of surgical treatment of fungal lesions of the middle ear, as well as postoperative cavities. In general, this topic is relevant for modern society, written in good language in compliance with all the rules for the publication of scientific works and is recommended for publication in the open press.

Results of hypofractionated stereotactic radiotherapy for resected and intact large brain metastases

To compare the results of post-resection or isolated HF-SRT in patients with LBMs. A prospective study included 115 patients with 129 intact LBMs and 133 patients with 149 resected LBMs who underwent HF-SRT. Median baseline focal size was 22.5 and 28 mm, median target volume - 8.3 and 23.7 cm3, respectively. Median follow-up was 13.9 months, median overall survival - 19.1 months. After 12 months, local recurrences developed in 17 and 31% of patients, respectively (p=0.0078). Local recurrence after 12 months developed in 23% of patients with residual tumor in postoperative cavity compared to 16% of patients after total resection (p=0.0073). After 12 months, incidence of leptomeningeal progression was 27 and 11%, respectively (p=0.033), incidence of symptomatic radiation-induced necrosis - 4 and 23%, respectively (p=0.0006). Post-resection HF-SRT demonstrated better local control and less severe symptomatic radiation-induced necrosis compared to patients with intact LBMs. Incidence of leptomeningeal progression is significantly higher after resection of LBMs.