Recurrent Soft Tissue Research Articles

Pediatric Metastatic Extracranial High-Grade Glioma: A Case Report and Literature Review

Abstract We report a case of a 10-year-old male with a right frontal diffuse pediatric-type high-grade glioma (HGG), H3-wildtype (WT) and IDH-WT, diagnosed at the age of 9 years, who underwent gross total resection, 60 Gy focal proton radiation in 30 fractions to the resection cavity with concurrent temozolomide followed by maintenance chemotherapy with temozolomide and lomustine. One month after completion of maintenance chemotherapy, he developed subcutaneous swelling in the right temporal region and was treated with antibiotics for presumed lymphadenitis. Two months later, he developed a recurrent painless right parietal soft tissue mass that failed to respond to antibiotic therapy. This prompted evaluation by MRI which revealed new enhancing masses in the cerebellum and extracranial soft tissue mass in right temporal region. He underwent gross total resection of both masses. Pathologic analysis confirmed both masses as recurrent HGG. Molecular markers, however, differed between the two sites of recurrence. He proceeded to complete hypofractionated proton therapy to sites of recurrence. Three months later he was found to have tumor dissemination into the spine and brain for which he received proton therapy to the whole spine and brain. Due to the presence of CDK4 amplification at diagnosis and at both sites of tumor recurrence, he then received palliative treatment with the CDK4/6 inhibitor, abemaciclib, for the final five months of his life. Since extracranial HGG is a rare presentation, with few cases reported in the pediatric population, we report this case and review previously published literature.

MO41-6 Chemotherapy for metastatic or recurrent soft tissue sarcoma: real-world experience in a single institute

MO41-6 Chemotherapy for metastatic or recurrent soft tissue sarcoma: real-world experience in a single institute

Virulence and resistance profiling of Staphylococcus aureus isolated from subclinical bovine mastitis in the Pakistani Pothohar region

Mastitis is considered one of the most widespread infectious disease of cattle and buffaloes, affecting dairy herds. The current study aimed to characterize the Staphylococcus aureus isolates recovered from subclinical mastitis animals in Pothohar region of the country. A total of 278 milk samples from 17 different dairy farms around two districts of the Pothohar region, Islamabad and Rawalpindi, were collected and screened for sub clinical mastitis using California Mastitis Test. Positive milk samples were processed for isolation of Staphylococcus aureus using mannitol salt agar. The recovered isolates were analyzed for their antimicrobial susceptibility and virulence genes using disc diffusion and PCR respectively. 62.2% samples were positive for subclinical mastitis and in total 70 Staphylococcus aureus isolates were recovered. 21% of these isolates were determined to be methicillin resistant, carrying the mecA gene. S. aureus isolates recovered during the study were resistant to all first line therapeutic antibiotics and in total 52% isolates were multidrug resistant. SCCmec typing revealed MRSA SCCmec types IV and V, indicating potential community-acquired MRSA (CA-MRSA) transmission. Virulence profiling revealed high prevalence of key genes associated with adhesion, toxin production, and immune evasion, such as hla, hlb, clfA, clfB and cap5. Furthermore, the Panton-Valentine leukocidin (PVL) toxin, that is often associated with recurrent skin and soft tissue infections, was present in 5.7% of isolates. In conclusion, the increased prevalence of MRSA in bovine mastitis is highlighted by this study, which also reveals a variety of virulence factors in S. aureus and emphasizes the significance of appropriate antibiotic therapy in combating this economically burdensome disease.

Abstract PO5-20-07: A Case of Metastatic Breast Cancer to Soft Tissue of the Thigh

Abstract Breast cancer is the most diagnosed cancer in women worldwide. The predominant cause of breast cancer mortality is metastatic disease with bone, lung, liver and brain being most common sites of metastasis. After melanoma, breast cancer is the most common cancer to have cutaneous metastatic disease and this presentation represents half of all cutaneous metastases. We are presenting a case of a 70-year-old female with distant recurrence of breast cancer to the left thigh. A 70-year-old female presented to clinic with a palpable left breast mass noted July 2022. Her medical history was notable for right sided upper lobe stage IIIB squamous cell lung cancer diagnosed in 2013 treated with chemotherapy and chest radiation (RT), menopause at 25 years old following TAH/BSO for fibroids. Family history included prostate cancer and genetic testing was negative for pathogenic mutation. Diagnostic mammogram showed a lesion in the left breast at 9:00 of 1.4 cm x 1.2 cm x1.4 cm, and biopsy showed grade 3 triple negative invasive ductal carcinoma (IDC). Her nodes were clinically and radiologically negative. She opted for breast conservation. In September of 2020 the patient had a left lumpectomy with sentinel lymph node biopsy. Final pathology (path) was pT1cN0 with two foci of IDC, grade 3, measuring 1.9 × 1.9 × 1.1 cm and 0.4 × 0.2 × 0.2 cm with negative margins. Two sentinel lymph nodes were negative for carcinoma. She received 4 cycles of doxorubicin and cyclophosphamide and started paclitaxel, but only completed 5/12 planned cycles. During these treatment cycles she was admitted twice for shortness of breath and found to have an exudative pleural effusion, repeat cytology was negative for malignancy at which point fluid did not recur. There was no CT evidence of lung nodules or plural thickening. Echocardiogram showed normal ejection fraction of 45%. PET scan was negative. Chemotherapy was stopped in February of 2021. Initial pre-operative discussion with radiation oncology indicated no contraindication to adjuvant RT. However, after simulation, it was deemed by radiation oncology that the patient was no longer a candidate for RT as during her lung cancer treatment, she had received RT of 69.4 Gy including the area of the current lumpectomy cavity. She then opted for bilateral mastectomy with immediate reconstruction in June 2021. Final path from both breasts showed no carcinoma. In November of 2021 she was admitted for shortness of breath and on CT scan was noted to have a left sided lung nodule. The patient declined biopsy and underwent a left wedge resection in January of 2022. Final path showed a 2.2. cm carcinoma consistent with breast primary that was ER 0, PR 0, and Her 2 neu 1+. She was started on capecitabine with plan for 6 months of treatment but stopped taking this after one month due to severe pain in her hands and feet. In November 2022 the patient noted a left thigh mass. Exam showed a firm, palpable thigh mass without overlying skin changes and core needle biopsy showed adenocarcinoma, favoring breast primary, ER 0, PR 0, HER 2 neu 2+ and FISH negative. PET scan showed no uptake in the chest abdomen or pelvis, however a 2.6 × 2.3 × 3.1 cm round mass in the left thigh was seen with SUV max of 8.6. She was started on traztuzumab-deruxtecan by medical oncology in December of 2022. The thigh tumor shrank significantly, however, patient discontinued after two infusions, citing intolerable hand weakness. She then received RT to the thigh. She was treated using 3D technique and 6 MV photons for a total dose of 5400 cGY, from February to March of 2023. Repeat PET June 2023 showed no avid uptake in the thigh. She has declined any additional systemic therapy. Soft tissue metastasis in distant recurrent breast cancer is uncommon and little guidance exists on clinical management. In cases of metastatic disease to the skin, hormone positive lesions can be managed with hormonal therapy. Early detection and biopsy for receptor studies may help guide therapy in cases of distant soft tissue recurrence. Citation Format: Rangel Melissa, Julia Alexieva, Alison Coogan, Lily Hussein, Elizabeth Marcus, Julie Wecsler. A Case of Metastatic Breast Cancer to Soft Tissue of the Thigh [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-20-07.

Characterisation of PVL-Positive Staphylococcus argenteus from the United Arab Emirates.

Staphylococcus argenteus is a recently described staphylococcal species that is related to Staphylococcus aureus but lacks the staphyloxanthin operon. It is able to acquire both resistance markers such as the SCCmec elements and mobile genetic elements carrying virulence-associated genes from S. aureus. This includes those encoding the Panton-Valentine leukocidin (PVL), which is associated mainly with severe and/or recurrent staphylococcal skin and soft tissue infections. Here, we describe the genome sequences of two PVL-positive, mecA-negative S. argenteus sequence type (ST) 2250 isolates from the United Arab Emirates in detail. The isolates were found in a dental clinic in the United Arab Emirates (UAE). Both were sequenced using Oxford Nanopore Technology (ONT). This demonstrated the presence of temperate bacteriophages in the staphylococcal genomes, including a PVL prophage. It was essentially identical to the published sequence of phiSa2wa_st78 (GenBank NC_055048), a PVL phage from an Australian S. aureus clonal complex (CC) 88 isolate. Besides the PVL prophage, one isolate carried another prophage and the second isolate carried two additional prophages, whereby the region between these two prophages was inverted. This "flipped" region comprised about 1,083,000 bp, or more than a third of the strain's genome, and it included the PVL prophage. Prophages were induced by Mitomycin C treatment and subjected to transmission electron microscopy (TEM). This yielded, in accordance to the sequencing results, one or, respectively, two distinct populations of icosahedral phages. It also showed prolate phages which presumptively might be identified as the PVL phage. This observation highlights the significance bacteriophages have as agents of horizontal gene transfer as well as the need for monitoring emerging staphylococcal strains, especially in cosmopolitan settings such as the UAE.

Giant cell tumor of bone at distal radius suffered more soft tissue recurrence and ultrasonography is effective to detect the soft tissue recurrence

BackgroundSoft tissue recurrence of giant cell tumor of bone (GCTB) is rare. This study aims to provide its prevalence, recurrent locations, risk factors, effective detection methods and a modified classification for this recurrence.MethodsPatients with soft tissue recurrence after primary surgery for GCTB were screened from January 2003 to December 2022. General data, recurrence frequency, types according to an original classification (type-I: peripheral ossification; type-II: central ossification; type-III: without ossification), a modified classification with more detailed subtypes (type I-1: ≤ 1/2 peripheral ossification; type I-2: ≥ 1/2 peripheral ossification; type II-1: ≤ 1/2 central ossification; type II-2: ≥ 1/2 central ossification; type III: without ossification), locations, detection methods such as ultrasonography, X-ray, CT or MRI, Musculoskeletal Tumor Society (MSTS) scores were recorded. Multivariate regression analysis was conducted to identify risk factors for recurrence frequency.ResultsA total of 558 recurrent cases were identified from 2009 patients with GCTB. Among them, 32 were soft tissue recurrence. The total recurrence rate was 27.78% (558/2009). Soft tissue recurrence rate was 5.73% among 558 recurrent cases, and 1.59% among 2009 GCTB patients, respectively. After excluding one patient lost to follow-up, 10 males and 21 females with the mean age of 28.52 ± 9.93 (16–57) years were included. The definitive diagnosis of all recurrences was confirmed by postoperative pathology. The interval from primary surgery to the first recurrence was 23.23 ± 26.12 (2–27) months. Eight recurrences occurred from primary GCTB located at distal radius, followed by distal femur (6 cases). Recurrence occurred twice in 12 patients and 3 times in 7 patients. Twenty-seven recurrences were firstly detected by ultrasonography, followed by CT or X-ray (10 cases in each). Types at the first recurrence were 5 cases in type-I, 8 in type-II and 18 in type-III. According to the modified classification, 3 patients in type I-1, 2 in type I-2, 1 in type II-1, 7 in type II-2, and 18 in type III. The mean MSTS score was 26.62 ± 4.21 (14—30). Neither Campanacci grade nor recurrence type, modified classification and other characters, were identified as risk factors.ConclusionsSoft tissue recurrence of GCTB may recur for more than once and distal radius was the most common location of primary GCTB that would suffer a soft tissue recurrence. Ultrasonography was a useful method to detect the recurrence. Since no risk factors were discovered, a careful follow-up with ultrasonography was recommended.

Durvalumab plus pazopanib combination in patients with advanced soft tissue sarcomas: a phase II trial

We aimed to determine the activity of the anti-VEGF receptor tyrosine-kinase inhibitor, pazopanib, combined with the anti-PD-L1 inhibitor, durvalumab, in metastatic and/or recurrent soft tissue sarcoma (STS). In this single-arm phase 2 trial (NCT03798106), treatment consisted of pazopanib 800 mg orally once a day and durvalumab 1500 mg once every 3 weeks. Primary outcome was overall response rate (ORR) and secondary outcomes included progression-free survival (PFS), overall survival, disease control rate, immune-related response criteria, and safety. The ORR was 30.4% and the trial met the pre-specified endpoint. The median PFS was 7.7 months (95% confidence interval: 5.7–10.4). The common treatment-related adverse events of grades 3–4 included neutropenia (9 [19.1%]), elevated aspartate aminotransferase (7 [14.9%]), alanine aminotransferase (5 [10.6%]), and thrombocytopenia (4 [8.5%]). In a prespecified transcriptomic analysis, the B lineage signature was a significant key determinant of overall response (P = 0.014). In situ analysis also showed that tumours with high CD20+ B cell infiltration and vessel density had a longer PFS (P = 6.5 × 10−4) than those with low B cell infiltration and vessel density, as well as better response (50% vs 12%, P = 0.019). CD20+ B cell infiltration was identified as the only independent predictor of PFS via multivariate analysis. Durvalumab combined with pazopanib demonstrated promising efficacy in an unselected STS cohort, with a manageable toxicity profile.

A comparative study of reconstruction modalities after knee joint-preserving tumor resection: reconstruction with a custom-made endoprosthesis versus reconstruction with a liquid nitrogen-inactivated autologous bone graft

BackgroundThis study evaluated the feasibility, complications, graft survival rate, and clinical outcomes of joint-preserving resection using a custom-made endoprosthesis and liquid nitrogen-inactivated autologous bone graft reconstruction in patients with malignant bone tumors around the knee joint.MethodsWe retrospectively analyzed 23 consecutive patients who underwent joint preservation surgery between 2008 and 2018 at our center. The study cohort included 13 patients who underwent custom-made endoprosthesis reconstruction and 10 who underwent liquid nitrogen-inactivated autologous bone graft reconstruction. The resected bone length, distance between the resection line and the joint, intraoperative blood loss, operation time, complications, and MSTS were compared between the two groups.ResultsThe median follow-up time was 68.5 months in the endoprosthesis group and 65.3 months in the inactivated autograft group. There were no significant differences in baseline characteristics, resected bone length, distance between the resection line and the joint, or intraoperative blood loss between the two groups. The operative time was longer in the inactivated bone graft group than in the endoprosthesis group (p < 0.001). The endoprosthesis group had more complications (six patients) and reoperations due to complications (five) than the inactivated autograft group (one), but there was no significant difference in the incidence of complications between the two groups (p = 0.158). The inactivated autograft group had one patient with type 1b complications, while the endoprosthesis group had one with type 1b complications, one with type 2b complications, and one with type 4a complications. One patient in the endoprosthesis group with type 5a complications experienced two soft tissue recurrences. The overall 5-year survival rate was 86.5% and the graft survival and final limb salvage rates were 100% in both groups. After the follow-up period, the mean MSTS scores were 91% ± 7% in the endoprosthesis group and 94% ± 6% in the inactivated autograft group, with no significant difference (p = 0.280).ConclusionJoint-preserving resection is a reliable and effective tumor resection method that can achieve good postoperative function. There were no significant differences in the incidence of complications, overall survival rate, or graft survival rate between the two groups.

Indicators of free radical oxidation in neutrophils of patients with primary and recurrent soft tissue sarcomas

Purpose of the study. To carry out a comparative analysis of lipid peroxidation intensity and antioxidant system indices in blood neutrophils of patients with primary and relapsed soft tissue sarcomas (STS) depending on sex and age.Patients and methods. Of the 81 patients included in the study, 48 had primary STS, 5 patients with continued growth, and 28 patients with recurrent STS. The patients were divided by sex and age; the level of lipid peroxidation products, superoxide dismutase (SOD) activity, total peroxidase activity (TPA), glutathione peroxidase (GPx) activity and reduced glutathione (RG) content in blood neutrophils were investigated by conventional spectrophotometric methods. The comparison groups (donors) consisted of 12 men and 17 women divided into the same age subgroups: ≤ 45 years and &gt; 45 years.Results. In donors, there was a multiple decrease in the SOD/TPA ratio with age, especially in women, and in men this was accompanied by an age-related decrease in GPx activity. In primary sarcomas in older women and in men with continued growth and recurrence, there was an increase in diene conjugates (DC). In men over 45 years of age, there was an increase in SOD, TPA, and GPx. Women of the older age group were characterized by activation of SOD and GPx, expressed in the relapsed process to a significantly greater extent than in men, and an increase in RG was observed in women. The increase in both components of the glutathione system and SOD activity was especially significant in the development of relapses in women for periods exceeding three years, which was accompanied by a decrease in DC content. Conclusions. Neutrophils are characterized by an increase in DC content in patients of both sexes in the older age group with primary and recurrent STS, with its highest content in men with continued growth and relapses. GPx activity, increased in both men and women in the older age group in all variants of STS development, may play an important role in the antioxidant protection of blood cells in STS. Thus, the most pronounced activation of GPx, accompanied by a maximum increase in reduced glutathione and activation of SOD, contributes to a decrease in the level of DC and the absence of MDA increase in women with slow development of recurrences.

Panton-Valentine leukocidin-induced neutrophil extracellular traps lack antimicrobial activity and are readily induced in patients with recurrent PVL + -Staphylococcus aureus infections.

Staphylococcus aureus strains that produce the toxin Panton-Valentine leukocidin (PVL-SA) frequently cause recurrent skin and soft tissue infections. PVL binds to and kills human neutrophils, resulting in the formation of neutrophil extracellular traps (NETs), but the pathomechanism has not been extensively studied. Furthermore, it is unclear why some individuals colonized with PVL-SA experience recurring infections whereas others are asymptomatic. We thus aimed to (1) investigate how PVL exerts its pathogenicity on neutrophils and (2) identify factors that could help to explain the predisposition of patients with recurring infections. We provide genetic and pharmacological evidence that PVL-induced NET formation is independent of NADPH oxidase and reactive oxygen species production. Moreover, through NET proteome analysis we identified that the protein content of PVL-induced NETs is different from NETs induced by mitogen or the microbial toxin nigericin. The abundance of the proteins cathelicidin (CAMP), elastase (NE), and proteinase 3 (PRTN3) was lower on PVL-induced NETs, and as such they were unable to kill S. aureus. Furthermore, we found that neutrophils from affected patients express higher levels of CD45, one of the PVL receptors, and are more susceptible to be killed at a low PVL concentration than control neutrophils. Neutrophils from patients that experience recurring PVL-positive infections may thus be more sensitive to PVL-induced NET formation, which might impair their ability to combat the infection.

Recurrent Soft Tissue Infections Associated With Burosumab Therapy in X-Linked Hypophosphatemic Rickets

Abstract X-linked hypophosphatemic rickets (XLH) is a genetic disorder characterized by elevated fibroblast growth factor 23 (FGF23), resulting in renal phosphate wasting and inadequate bone mineralization. Burosumab, a monoclonal antibody that inhibits FGF23 activity, has shown promise in improving renal phosphate reabsorption and clinical outcomes in XLH patients. However, the potential side effects of burosumab, particularly its impact on immune function and susceptibility to infections, remain a subject of concern. In this case report, we describe a 57-year-old male individual with XLH who experienced recurrent soft tissue infections while receiving burosumab therapy. The infections included an olecranon abscess, a cervical retropharyngeal phlegmon with a sternocleidomastoid abscess, and suprapubic cellulitis, all of which were treated with antibiotic therapy. Following discontinuation of burosumab therapy, the patient did not experience further soft tissue infections. These observations suggest a potential association between burosumab therapy and an increased risk of soft tissue infections. Mechanistically, disruption of the FGF23-Klotho signaling axis may lead to impaired humoral immunity mediated by B lymphocytes and compromised innate immune response mediated by macrophages. Further investigation is warranted to better understand the immunological effects of burosumab and its implications for infectious complications in XLH patients.

Giant cell tumors of the distal ulna: long-term recurrence rate and functional outcomes of en bloc resection versus curettage in a multicenter study

ObjectiveThe wrist is the second most commonly involved location for GCTB, while distal ulna is a relatively rare location and limited evidence exists on which surgical approaches and reconstruction techniques are optimal. We carried out a multicenter retrospective study to evaluate the recurrence rate of distal ulna GCTB and the long-term functional outcomes of different surgery options.MethodsAll 28 patients received surgical treatment for distal ulna GCTB in one of three tertiary bone tumor centers between May 2007 and January 2021 with a minimum two-year follow-up. Surgical options included intralesional curettage or en bloc resection (one of 3 types). Functional outcomes were assessed by the MSTS score, the QuickDASH instrument, MWS, and MHQ according to the latest treatment.ResultsOverall recurrence rate was 14.2%. The curettage group (N = 7) had a significantly higher recurrence rate compared to en bloc resection (N = 21) (42.9% vs 4.8%) (mean follow-up: 88.8 mo). Seven patients received the Darrach procedure, 5 received the original Sauvé–Kapandji procedure, and 9 received the modified Sauvé–Kapandji procedure with extensor carpi ulnaris (ECU) tenodesis. Of the 4 patients having a recurrence, 1 received the Darrach EBR, 2 received the modified Sauvé–Kapandji procedure, and 1 received resection for soft tissue recurrence. Only MWS and esthetics in the MHQ scores were different (curettage, Darrach, Sauvé–Kapandji, and Sauvé–Kapandji with ECU tenodesis [MWS: 96.5 ± 1.3 vs 91.5 ± 4.7 vs 90.8 ± 2.8 vs 91.5 ± 3.6; esthetics in MHQ: 98.5 ± 3.1 vs 89.9 ± 4.7 vs 93.8 ± 4.4 vs 92.6 ± 3.8], respectively).ConclusionsEn bloc resection for distal ulna GCTB had a significantly lower recurrence rate compared with curettage and achieved favorable functional outcome scores. Given the higher recurrence rate after curettage, patients should be well informed of the potential benefits and risks of selecting the distal radioulnar joint-preserving procedure. Moreover, reconstructions after tumor resection of the ulna head do not appear to be necessary.

Hepatic safety and efficacy of immunomodulatory drugs used in patients with autoimmune hepatitis

Background and aimsThere is little data on the hepatic efficacy and safety of immunomodulatory drugs used in patients with autoimmune hepatitis (AIH), despite their established use in dermatology, rheumatology and inflammatory bowel diseases (IBD). Our aim was to collect real-life data on the experience of expert centres in treating AIH patients with these drugs, considered unconventional for AIH management. MethodsOnline survey among hepatology centres being part of the European Reference Network on Hepatological Diseases (ERN RARE-LIVER). Results25 AIH patients have been reported. Ten were female, median age at diagnosis was 28 years; median follow-up was 17 months. All had initially received AIH-standard treatment.AIH-unconventional treatment was initiated for concomitant autoimmune diseases in 15 cases: nine for IBD (five vedolizumab and four ustekinumab), and one each for following diseases: autoinflammatory syndrome (tocilizumab), chronic urticaria (omalizumab), rheumatoid arthritis (abatacept), psoriasis (guselkumab), psoriatric arthritis (secukinumab, followed by ustekinumab) and alopecia (ruxolitinib). Three patients were treated with immunomodulatory drugs for side effects of previous treatments, including two patients with IBD treated with vedolizumab and ustekinumab, respectively, and one treated with belimumab. At the end of follow-up, 13 patients were in complete biochemical response, the patient on omalizumab had a relapse, and four patients with concomitant IBD had insufficient response.Seven patients were treated for lack of biochemical remission, of whom six with belimumab, all initially reaching complete biochemical response, but five relapsing during follow-up; and one with secukinumab, having concomitant rheumatoid arthritis and ankylosing spondylitis, reaching complete biochemical response.Only the patient on abatacept received unconventional treatment as monotherapy. Side effects were reported in two patients on belimumab: one recurrent soft tissue infections, one fatigue and arthralgia. ConclusionAmong 25 AIH patients who were treated with immunomodulatory drugs for different reasons, the majority had a fovorable course, relapse was frequent in difficult-to-treat patients who received belimumab, and four with concomitant IBD had insufficient response.

Grade shifts in recurrent canine soft tissue sarcomas and mast cell tumors.

To determine the incidence of histologic grade shift (alteration of grade relative to the original tumor) in recurrent canine soft tissue sarcoma (STS) and mast cell tumor (MCT), and to determine the level of agreement between blinded pathologist review and original histology interpretation of STS and MCT grades. 15 dogs with recurrent cutaneous/subcutaneous STS and 5 dogs with recurrent cutaneous MCT. All included dogs underwent excision of both the primary and recurrent tumors and had tumor samples available for review. The medical records and histology database from a single institution were reviewed, and data were recorded and analyzed. A single board-certified veterinary pathologist performed blinded evaluation of all excisional tumor samples, including both primary and recurrent disease, and these were evaluated independently and in conjunction with initial pathologic diagnoses. Based on single pathologist review, 7 of 15 (46.7%) dogs with recurrent STS had grade shift characterized by a higher or lower recurrent tumor grade in 4 of 7 and 3 of 7 cases, respectively, and 1 of 5 dogs with recurrent MCT had grade shift characterized by an increased grade of the recurrent tumor. Variability in reported grade between original histology report and pathologist review occurred for 13 of 30 (43.3%) STS excisional biopsy samples and 0 of 10 MCT excisional biopsy samples. Grade shift has been reported in multiple tumor types in people and has the potential to alter prognosis and treatment recommendations. This is the first study to document this phenomenon in dogs. Additional large-scale studies are needed to determine factors associated with grade shift as well as prognostic significance of grade shift for recurrent canine STS and MCT.

Using a CT-based scale to evaluate disease extension and the resectability of locally advanced thyroid cancer.

To establish a computed tomography (CT)-based scale to evaluate the resectability of locally advanced thyroid cancer. This twin-centre retrospective study included 95 locally advanced thyroid cancer patients from the 1st centre as the training cohort and 31 patients from the 2nd centre as the testing cohort, who were categorised into the resectable and unresectable groups. Three radiologists scored the CT scans of each patient by evaluating the extension to the recurrent laryngeal nerve (RLN), trachea, oesophagus, artery, vein, soft tissue, and larynx. A 14-score scale (including all comprised structures) and a 12-score scale (excluding larynx) were developed. Receiver-operating characteristic (ROC) analysis was used to evaluate the performance of the scales. Stratified fivefold cross-validation and external verification were used to validate the scale. In the training cohort, compromised RLN (p < 0.001), trachea (p = 0.001), oesophagus (p = 0.002), artery (p < 0.001), vein (p = 0.005), and soft tissue (p < 0.001) were predictors for unresectability, while compromised larynx (p = 0.283) was not. The 12-score scale (AUC = 0.882, 95%CI: 0.812-0.952) was not inferior to the 14-score scale (AUC = 0.891, 95%CI: 0.823-0.960). In subgroup analysis, the AUCs of the 12-score scale were 0.826 for treatment-naïve patients and 0.976 for patients with prior surgery. The 12-score scale was further validated with a fivefold cross-validation analysis, with an overall accuracy of 78.9-89.4%. Finally, external validation using the testing cohort showed an AUC of 0.875. The researchers built a CT-based 12-score scale to evaluate the resectability of locally advanced thyroid cancer. Validation with a larger sample size is required to confirm the efficacy of the scale. This 12-score CT scale would help clinicians evaluate the resectability of locally advanced thyroid cancer. • The researchers built a 12-score CT scale (including recurrent laryngeal nerve, trachea, oesophagus, artery, vein, and soft tissue) to evaluate the resectability of locally advanced thyroid cancer. • This scale has the potential to help clinicians make treatment plans for locally advanced thyroid cancer.

Vulvovaginitis due to methicillin-resistant and methicillin-sensitive Staphylococcus aureus among women in reproductive age-group

Abstract Background: Although Staphylococcus aureus is commensal in 20% of individuals, its pathogenic consequences have not been unidentified. Colonisation of methicillin-resistant S. aureus (MRSA) in the vagina is associated with recurrent vaginal infections, skin and soft tissue infections surrounding the genital and buttock area and infertility. Methods: This study aimed at identifying S. aureus in vaginitis and the antibiotic susceptibility of S. aureus. Results: Of 463 patients’ vaginal swabs, 53 had significant growth, yielding 60 aerobic bacterial isolates. Seven (15%) isolates were S. aureus, 78% were MRSA and 100% were resistant to penicillin. All were sensitive to doxycycline and linezolid. Because the vaginal cavity is a reservoir for S. aureus, genital infections are considered, especially if they are recurring. Conclusions: Among patiens with vaginitis, MRSA is a common aetiological cause and should be tested for.

Outcome of Limb Salvaging Procedure for Bone Tumor Using Liquid Nitrogen Technique: A Case Series of 21 Patients

Abstract Introduction and importance: Autologous bone graft treated with liquid nitrogen is an option for biological reconstruction of bone defects in patients receiving tumor resection. This is the first report in Hong Kong on the outcome of this biological reconstruction in terms of functional outcome, local recurrence rate, and prognosis. Case presentation: From 2015 to 2021, 21 patients with bone tumor resection and reconstruction using liquid nitrogen treated autologous bone graft were recruited. The medical records and radiological images were retrieved for retrospective review. After delivery of the specimen, all the soft tissue of the excised bone was removed at the back table before cryotherapy. The auto graft was immersed in liquid nitrogen for 20 minutes, and thawed at room temperature for 10 minutes. After that the autograft was immersed in distilled water for 15 minutes before being incorporated into the reconstruction. All of them were followed up for at least one year post-operation. Clinical discussion: The mean union time was 13.3 months (from 4 to 31 months). The mean Musculoskeletal Tumor Society (MSTS) score was 22.6 (from 12 to 30). The mean follow up time was 38.2 months (from 12 to 64 months). There were two local soft tissue recurrences and one local recurrence from host bone. Conclusion: Autologous bone graft treated with liquid nitrogen is a safe option for biological reconstruction of bone defects after tumor resection. It provides satisfactory outcomes with low local recurrence rate, as well as comparable complications with other reconstruction methods.

Effect of segmental versus marginal mandibular resection on local and lymph node recurrences in oral squamous cell carcinoma: is tumorous bone infiltration or location and resulting soft tissue recurrences a long-term problem?

Oral squamous cell carcinomas (OSCCs) adjacent to the mandible or with clinically suspected bone infiltration are surgically treated either with marginal or segmental resections. This retrospective study compared both resections regarding local recurrence and lymph node recurrence or secondary lymph node metastases. All consecutive primary OSCC cases between January 2007 and December 2015 that underwent mandibular marginal or segmental resection were included. Rates of local and lymph node recurrences or secondary metastases and possible risk factors such as tumor localization according to Urken's classification were recorded. In total, 180 patients with 85 marginal (group I) and 95 segmental (group II) mandibular resections were analyzed. The local recurrence rates were comparable between the groups (28.2% vs. 27.4%; p = 0.897). Lymph node recurrences or secondary metastases were higher in group I (9.4% (n = 8) vs. 6.2% (n = 6); p = 0.001). Tumor localization appears to affect the outcomes. Significantly fewer local and lymph node recurrences/metastases were found for Urken's classification SB and S calculated by two-proportion z-test (p = 0.014 and 0.056, respectively). Local recurrences mostly emerged from soft tissues, which should be resected more radically than the bones. While bone infiltration appears technically well controllable from an oncologic point of view, local recurrences and lymph node recurrences/metastases remain an issue. Regular clinical aftercare with imaging is crucial to detect recurrences.

What Is the Prosthetic Survival After Resection and Intercalary Endoprosthetic Reconstruction for Diaphyseal Bone Metastases of the Humerus and Femur?

Large metastatic lesions of the diaphysis can cause considerable pain and result in difficult surgical challenges. Resection and cemented intercalary endoprosthetic reconstruction offer one solution to the problem, but it is an extensive operation that might not be tolerated well by a debilitated patient. The risk of aseptic loosening and revision after intercalary endoprosthetic replacement has varied in previous reports, which have not examined the risk of revision in the context of patient survival. (1) In a small case series from one institution, what is the survivorship of patients after cemented intercalary endoprosthetic replacement for diaphyseal metastasis, and what is the cumulative incidence of revision for any reason? (2) What are the complications associated with cemented intercalary reconstruction? (3) What is the functional outcome after the procedure as assessed by the MSTS93 score? We retrospectively studied 19 patients with diaphyseal long bone metastases who were treated with resection and cemented intercalary endoprosthetic reconstruction by five participating surgeons at one referral center from 2006 to 2017. There were 11 men and eight women with a median age of 59 years (range 46 to 80 years). The minimum follow-up required for this series was 12 months; however, patients who reached an endpoint (death, radiographic loosening, or implant revision) before that time were included. One of these 19 patients was lost to follow-up but was not known to have died. The median follow-up was 24 months (range 0 to 116 months). Eight of the 19 patients presented with pathologic fractures. Ten of 19 lesions involved the femur, and nine of 19 were in the humerus. The most common pathologic finding was renal cell carcinoma (in 10 of 19). Survival estimates of the patients were calculated using the Kaplan-Meier method. A competing risks estimator was used to evaluate implant survival, using death of the patient as the competing risk. We also estimated the cumulative incidence of aseptic loosening in a competing risk analysis. Radiographs were analyzed for radiolucency at the bone-cement-implant interfaces, fracture, integrity of the cement mantle, and component position stability. Complications were assessed using record review that was performed by an individual who was not involved in the initial care of the patients. Functional outcomes were assessed using the MSTS93 scoring system. Patient survivorship was 68% (95% CI 50% to 93%) at 1 year, 53% (95% CI 34% to 81%) at 2 years, and 14% (95% CI 4% to 49%) at 5 years; the median patient survival time after reconstruction was 25 months (range 0 to 116 months). In the competing risk analysis, using death as the competing risk, the cumulative incidence of implant revision was 11% (95% CI 2% to 29%) at 1 year and 16% (95% CI 4% to 36%) at 5 years after surgery; however, the cumulative incidence of aseptic loosening (with death as a competing risk) was 22% (95% CI 6% to 43%) at 1 year and 33% (95% CI 13% to 55%) at 5 years after surgery. Other complications included one patient who died postoperatively of cardiac arrest, one patient with delayed wound healing, two patients with bone recurrence, and one patient who experienced local soft tissue recurrence that was excised without implant revision. Total MSTS93 scores improved from a mean of 12.6 ± 8.1 (42% ± 27%) preoperatively to 21.5 ± 5.0 (72% ± 17%) at 3 months postoperatively (p < 0.001) and 21.6 ± 8.5 (72% ± 28%) at 2 years postoperatively (p = 0.98; 3 months versus 2 years). Resection of diaphyseal metastases with intercalary reconstruction can provide stability and short-term improvement in function for patients with advanced metastatic disease and extensive cortical destruction. Aseptic loosening is a concern, particularly in the humerus; however, the competing risk analysis suggests the procedure is adequate for most patients, because many in this series died of disease without undergoing revision. Level IV, therapeutic study .

Abstract 203: A characterization of drug sensitivity and resistance in sarcoma

Abstract Bone and soft tissue sarcomas are a rare and diverse family of malignancies. Sarcomas disproportionally impact young patients, and most subtypes have limited therapeutic options. Given the rarity of these tumors and their heterogenous nature, there is a need for developing clinically relevant models to broadly characterize the landscape of drug resistance and sensitivity in sarcoma in order to identify effective therapies. We leverage patient-derived tumor organoids (PDTOs) to create models across an array of bone and soft tissue sarcomas. We have procured n=193 specimens from n=127 patients undergoing biopsies or surgical resections at UCLA Health hospitals and successfully generated PDTOs from over 100 samples so far originating from primary, recurrent, or metastatic bone and soft tissue sarcomas. We performed molecular and histologic characterization to compare the PDTOs with the parent tumor and monitored PDTOs growth using a machine learning-based imaging pipeline (Al Shihabi et al, 2022). Our results show that sarcoma PDTOs closely resemble the tumor of origin in their molecular features and exhibit diverse growth patterns across subtypes. We leveraged our existing organoid high-throughput drug screening pipeline (Phan et al, 2019) to perform functional screenings of chemotherapies, targeted agents, and combination therapies, with results within one week from surgery. By screening a large number of samples, we could identify patterns of response with respect to diagnosis, prior treatment, patient age, lesion type, and disease trajectory. We observe tumor-specific susceptibilities with high heterogeneity both across and within sarcoma subtypes. As an example, we will focus on osteosarcoma, a bone tumor common in the pediatric and AYA population. We characterized PDTOs from n=33 osteosarcoma specimens and observed significant heterogeneity in response to NCCN-recommended therapies, suggesting that some patients may benefit from a personalized selection of approved therapeutic regimens. Finally, we compare functional and genomic screening to show how drug sensitivity and resistance characterization can facilitate optimal drug selection, avoid ineffective therapies, and mirror patient outcomes. Citation Format: Ahmad Al Shihabi, Peyton J. Tebon, Huyen T. Nguyen, Jomjit Chantharasamee, Sara Sartini, Ardalan Davarifar, Alexandra Jensen, Miranda Diaz-Infante, Hannah Cox, Alfredo Gonzalez, Nasrin Tavanaie, Sarah Dry, Arun Singh, Bartosz Chmielowski, Joseph G. Crompton, Anusha Kalbasi, Fritz C. Eilber, Francis J. Hornicek, Nicholas Bernthal, Scott D. Nelson, Paul C. Boutros, Noah Federman, Jane Yanagawa, Alice Soragni. A characterization of drug sensitivity and resistance in sarcoma [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 203.