Bone Involvement Research Articles

Hematologic toxicity in 177lu-PSMA-617 treatment for mCRPC: Unraveling the impact of PSMA PET bone tumor volume (PSMA-bTTV).

5075 Background: Lutetium-177 prostate-specific membrane antigen (177Lu-PSMA-617) is a life-prolonging treatment approved by the FDA in metastatic castration-resistant prostate cancer (mCRPC), at a very late stage when there frequently reduced bone marrow reserve. We aim to report the incidence of hematologic toxicity during treatment and potential risk factors in a single-center study. Methods: This retrospective single-institution case series included mCRPC patients who underwent at least one cycle of 177Lu-PSMA-617 treatment between June 2022 and January 2024. Hematological parameters were documented at baseline, 3 weeks after each treatment, and before each subsequent treatment administration. Then, we captured the nadir values for each parameter during treatment. Hematologic toxicities were assessed using the Common Terminology Criteria for Adverse Events v5.0, with Grades 3 and 4 considered significant. Multivariable logistic regression analyses were conducted to investigate the association between hematological adverse events and baseline characteristics including PSMA-bTTV, measured by semi-automatic contouring of the PSMA-expressing whole-body bone metastases on pre-treatment PSMA PET. Results: Our study included 138 mCRPC patients (median age: 73y, prior chemotherapy: 92%, prior radiation: 43.5%, bone involvement: 89.1%), who underwent a median of 3 cycles (IQR: 2-5) of 177Lu-PSMA-617 treatment. At baseline, 8 (5.8%) patients had grade 3 anemia, 2 (1.4%) patients had grade 3 leukopenia, and 1 (0.7%) patient had grade 3 thrombocytopenia. Nadir values during treatment indicated that 23 (16.7%) had grade 3 anemia, 5 (3.6%) had grade 3 leukopenia, and 11 (8%) had grade 3 and 4 thrombocytopenia. Multivariable analysis of predisposing factors for hematologic adverse events showed that the PSMA-bTTV was significantly associated with occurrence of any grade ≥3 hematologic toxicity, anemia, and thrombocytopenia after adjusting for other baseline clinical variables (Table). Conclusions: Over 1 in 5 patients with mCRPC experienced significant hematologic adverse events during treatment with 177Lu-PSMA-617. Bone tumor volume is a possible risk factor for developing significant hematologic toxicity. [Table: see text]

Stratified Treatment in Pediatric Anaplastic Large Cell Lymphoma: Result of a Prospective Open-Label Multiple-Institution Study.

The risk stratification of pediatric anaplastic large cell lymphoma (ALCL) has not been standardized. In this study, new risk factors were included to establish a new risk stratification system for ALCL, and its feasibility in clinical practice was explored. On the basis of the non-Hodgkin's lymphoma Berlin-Frankfurt-Munster 95 (NHL-BFM-95) protocol, patients with minimal disseminated disease (MDD), high-risk tumor site (multiple bone, skin, liver, and lung involvement), and small cell/lymphohistiocytic (SC/LH) pathological subtype were enrolled in risk stratification. Patients were treated with a modified NHL-BFM-95 protocol combined with an anaplastic lymphoma kinase inhibitor or vinblastine (VBL). A total of 136 patients were enrolled in this study. The median age was 8.8 years. The 3-year event-free survival (EFS) and overall survival of the entire cohort were 77.7% (95% confidence interval [CI], 69.0% to 83.9%) and 92.3% (95% CI, 86.1% to 95.8%), respectively. The 3-year EFS rates of low-risk group (R1), intermediate-risk group (R2), and high-risk group (R3) patients were 100%, 89.5% (95% CI, 76.5% to 95.5%), and 67.9% (95% CI, 55.4% to 77.6%), respectively. The prognosis of patients with MDD (+), stage IV cancer, SC/LH lymphoma, and high-risk sites was poor, and the 3-year EFS rates were 45.3% (95% CI, 68.6% to 19.0%), 65.7% (95% CI, 47.6% to 78.9%), 55.7% (95% CI, 26.2% to 77.5%), and 70.7% (95% CI, 48.6% to 84.6%), respectively. At the end of follow-up, one of the five patients who received maintenance therapy with VBL relapsed, and seven patients receiving anaplastic lymphoma kinase inhibitor maintenance therapy did not experience relapse. This study has confirmed the poor prognostic of MDD (+), high-risk site and SC/LH, but patients with SC/LH lymphoma and MDD (+) at diagnosis still need to receive better treatment (ClinicalTrials.gov number, NCT03971305).

Acute Tuberculous Appendicitis, a Rare Entity

Tuberculous appendicitis is a rare disease, with an overall incidence of between 1.5-3.0% among tuberculosis patients. It was first described by Corbin et al in 1873 and since then has been rarely recorded in publications and case reports. In the USA, extrapulmonary disease is seen in around 20-30% of tuberculosis patients, with the most common extrapulmonary manifestations being bone (30%), urinary tract (24%) and lymph node (13%) involvement. A high index of suspicion is required to make the diagnosis of appendicular tuberculosis, although it can cause damage to the appendix without other signs of localized disease. We report a case of a woman diagnosed with primary tuberculous appendicitis in a patient with human immunodeficiency virus (HIV), with evidence of extra-intestinal disease.

Construction and validation of a risk prediction model for early hungry bone syndrome in maintenance hemodialysis patients post-parathyroidectomy.

Parathyroidectomy (PTX) is an effective treatment for refractory secondary hyperparathyroidism (SHPT), but it can lead to hungry bone syndrome (HBS), significantly threatening the health of maintenance haemodialysis (MHD) patients. While previous studies have analyzed the risk factors for HBS post-PTX, the predictive performance and clinical applicability of these risk models need further validation. This study aims to construct and validate a risk prediction model for HBS in MHD patients with SHPT post-PTX. A retrospective analysis was conducted on 368 MHD patients with SHPT who underwent PTX at Changsha Jieao Nephrology Hospital from January 2020 to December 2021. Patients were divided into a HBS group and a non-HBS group based on the occurrence of HBS. General data, surgical information, and biochemical indicators were compared between the 2 groups. Multivariate logistic regression was used to identify factors influencing HBS, and a risk prediction model was established. The model's performance was evaluated using receiver operator characteristic (ROC) curves, decision curves, and calibration curves. External validation was performed on 170 MHD patients with SHPT who underwent PTX at the Third Xiangya Hospital of Central South University from January to December 2022. The incidence of HBS post-PTX in MHD patients with SHPT was 60.60%. Logistic regression analysis identified preoperative bone involvement (OR=3.908, 95% CI 2.179 to 7.171), preoperative serum calcium (OR=7.174, 95% CI 2.291 to 24.015), preoperative intact parathyroid hormone (iPTH) (OR=1.001, 95% CI 1.001 to 1.001), preoperative alkaline phosphatase (ALP) (OR=1.001, 95% CI 1.000 to 1.001), and serum calcium on the first postoperative day (OR=0.006, 95% CI 0.001 to 0.038) as independent risk factors for HBS (all P<0.01). The constructed risk prediction model demonstrated good predictive performance in both internal and external validation cohorts. The internal validation cohort showed an accuracy of 0.821, sensitivity of 0.890, specificity of 0.776, Youden index of 0.666, and area under the curve (AUC) of 0.882 (95% CI 0.845 to 0.919). The external validation cohort showed an accuracy of 0.800, sensitivity of 0.806, specificity of 0.799, Youden index of 0.605, and AUC of 0.863 (95% CI 0.795 to 0.932). Preoperative bone involvement, serum calcium, iPTH, ALP, and serum calcium on the first postoperative day are influencing factors for HBS in MHD patients with SHPT post-PTX. The constructed risk prediction model based on these factors is reliable.

#99 Clinical characteristics and outcomes of PTLD after kidney transplant: a single center experience

Abstract Background and Aims Post-Transplant Lymphoproliferative Disorder (PTLD) is a serious and potentially fatal complication of immunosuppression in kidney transplantation. Given the rarity of this entity, a high index of suspicion is necessary. We aimed to review the incidence, clinical presentation, histological subtypes, treatment, patient and graft survival of PTLD in kidney transplant patients in our unit. Methods Observational retrospective study, including adults diagnosed with PTLD between 1998 and 2023 in a Kidney Transplantation Center. Results Of 1390 kidney transplant recipients, 4 (0.3%) developed PTLD with a mean age of 52 ± 12.5 years. All cases were late-onset, occurring one year after transplantation with a median time from transplantation to diagnosis of 16.7 ± 7.3 years (range: 5-22 years). Of these, none had EBV donor/recipient mismatch. Two patients had prior rejection episodes (one patient, acute T cell-mediated rejection and the other patient, acute T cell-mediated rejection and active antibody mediated rejection). Clinical presentation was variable. Non-specific constitutional symptoms such as fever, fatigue and night sweats were present in all patients. Organ-specific symptoms were also present: lumbar pain in one patient with bone involvement, and delirium and lethargy in two patients with central nervous system involvement. Laboratory analyses revealed an increase in serum LDH in all patients. The primary sites of involvement were central nervous system (50%), lymph nodes (25%) and bone (25%). At PTLD diagnosis, immunosuppression included: tacrolimus (100%), mycophenolate mofetil (75%), low-dose of steroids (50%) and everolimus (25%). Regarding histologic classification, 75% were monomorphic and 25% polymorphic. In the monomorphic group, all patients had Diffuse Large B Cell Lymphoma (CD20 positive). In the polymorphic group, the patient had a Mixed Cellularity Classic Hodgkin Lymphoma (CD20 negative). Immunosuppression therapy was reduced in all patients with discontinuation of mycophenolate mofetil and tacrolimus. In the patient who was taking everolimus, the dose was increased due to the potential clinical antitumor effects of mTOR inhibition. Additional therapies included, rituximab in monotherapy or in combination with chemotherapy (R-CHOP) in the monomorphic group. Palliative measures were selected for one patient of this group due to advanced disease. The patient with Mixed Cellularity Classic Hodgkin Lymphoma (CD20 negative) did chemotherapy with ABVD. None of the patients underwent surgery or radiation therapy. Two patients needed dialysis. Three patients died in the first four weeks after PTLD diagnosis, all due to infectious complications. Patient survival was 25% one year after diagnosis. Conclusions Although the incidence of PTLD was low following kidney transplantation, its impact was significant in kidney graft and overall patient survival. Given the poor prognosis, new therapies combining high efficacy and low toxicity are an urgent unmet medical need in this field.

Retrospective Evaluation of Radiological Findings in Patients with Oral Malignancy

Aim: Oral cancer ranks among the most prevalent cancers worldwide. Imaging methods play a vital role in assessing patients. This study aimed to evaluate the age, sex, and localization distribution as well as panoramic and cone-beam computed tomography (CBCT) image findings in patients with oral malignancy with bone involvement. Materials and Method: Patients who were histopathologically diagnosed with malignant oral lesions at Gazi University, Faculty of Dentistry, Department of Oral Pathology between 2009 and 2023 were reviewed. Patients with oral malignancies whose panoramic images or CBCT images were available in the radiology archive were included in this study. Age-sex distribution was recorded. Localization of lesions and radiological features such as internal structures, borders, and effects on surrounding tissues were evaluated. Results: The mean age of the patients was 58.2 years; nine of them were female and thirteen were male. The incidence of malignancies included in this study was higher in men than in women, and the mandible/maxilla ratio was equal. The most common primary tumor was squamous cell carcinoma (SCC) (n=12). SCC lesions caused destruction in the cortical borders of neighboring structures in the region where they were located and showed the potential to spread toward these regions. Mucoepidermoid carcinoma was observed as an unilocular radiolucent lesion with clear borders, and it was determined that it destroyed the cortical bone. Conclusion: Panoramic radiography and CBCT images are valuable imaging methods in the evaluation of bone involvement of oral malignancies.

Secondary cardiac lymphoma presenting with cardiac tamponade and cardiac mass: a case report

BackgroundCardiac tamponade as the presenting manifestation of systemic lymphoma is relatively uncommon. Pericardium is the commonest site of involvement in secondary malignancies with systemic lymphoma involving the heart in 20% of the cases.Case presentationWe describe a case of a 78-year-old gentleman, who presented with symptoms of new onset cardiac failure, and hemodynamic compromise. An echocardiography revealed cardiac tamponade, necessitating an emergency pericardiocentesis. With the aid of multimodality imaging, he was found to have a right atrioventricular groove mass, widespread lymph node enlargement with bone and peritoneal involvement. Ultimately, a histopathological evaluation revealed a diagnosis of Diffuse Large B Cell Lymphoma (DLBCL).ConclusionsOur case illustrates that a patient with DLBCL may present with cardiac tamponade as a result of metastasis. This diagnosis, although rare, is likely to be missed, which can cause fatal complications, such as cardiac tamponade, fatal arrhythmias or sudden cardiac death.

Genetic Landscape and Its Prognostic Impact in Children With Langerhans Cell Histiocytosis.

Langerhans cell histiocytosis (LCH) is a rare myeloid neoplasm that predominantly affects young children. To investigate genetic alterations and their correlation with clinical characteristics and prognosis in pediatric LCH. We performed targeted sequencing to detect mutations in LCH lesions from pediatric patients. A total of 30 genomic alterations in 5 genes of the MAPK pathway were identified in 187 of 223 patients (83.9%). BRAF V600E (B-Raf proto-oncogene, serine/threonine kinase) was the most common mutation (51.6%), followed by MAP2K1 (mitogen-activated protein kinase kinase 1) alterations (17.0%) and other BRAF mutations (13.0%). ARAF (A-Raf proto-oncogene, serine/threonine kinase) and KRAS (KRAS proto-oncogene, GTPase) mutations were relatively rare (2.2% and 0.9%, respectively). Additionally, FNBP1 (formin-binding protein 1)::BRAF fusion and MAP3K10 (mitogen-activated protein kinase kinase 10) mutations A17T and R823C were identified in 1 case each, with possible constitutive activation of ERK1/2 phosphorylation. BRAF V600E was more frequent in patients with risk organ involvement, while MAP2K1 mutation was more prevalent in patients with single-system LCH (P = .001). BRAF V600E was associated with craniofacial bone, skin, liver, spleen, and ear involvement (all P < .05). Patients with other BRAF mutations had a higher proportion of spinal column involvement (P = .006). Univariate analysis showed a significant difference in progression-free survival among the 4 molecular subgroups for patients treated with first-line therapy (P = .02). According to multivariate analysis, risk organ involvement was the strongest independent adverse prognostic factor (hazard ratio, 8.854; P < .001); BRAF or MAP2K1 mutation was not an independent prognostic factor. Most pediatric patients with LCH carry somatic mutations involving the MAPK pathway, correlating with clinical characteristics and outcomes for first-line chemotherapy.

Challenges in the Assessment of Medullary Bone Invasion in Oral Cavity Cancers and Its Prognostic Significance.

As per AJCC 8th edition TNM staging system, bone invasion is a poor prognostic marker that upstages oral cavity squamous carcinoma (OSCC) to pT4a. Cortical erosion alone of bone or tooth socket by a gingival primary is not sufficient to upstage a tumour. The differentiation of cortical erosion from invasion through the cortical bone into the medulla is often challenging, limiting accurate staging. This review aims to assess the difficulties in differentiating cortical erosion from medullary invasion and evaluate the prognostic significance of different patterns of bone involvement. A retrospective review of OSCC with primary curative surgery and bone resection treated at a single-center over 10years, was performed to assess the prognostic significance of bone invasion. Hematoxylin-eosin stained slides of a subset of cases were re-reviewed in a planned manner to assess difficulties in precise categorization (no invasion/erosion/cortical invasion and medullary invasion), evaluate interobserver agreement, and correlate with clinical outcome. Five hundred and ninety patients were included, with a median follow-up of 28months. On univariate analysis, the 3-year local, nodal and distant metastasis control were not significantly different in the 3 groups of no invasion, erosion, and invasion (p = 0.43, 0.47, and 0.47, respectively). Overall survival (OS) at 3years was 78.1% and disease-free-survival(DFS) was 63.7% in the entire cohort. On univariate analysis, there was significant difference in OS and DFS based on these groups. This did not translate into independent prognostic benefit on multivariable analysis (p = 0.75 and 0.19, respectively). The independent prognostic factors were margin positivity, tumor differentiation, perineural invasion and pathological nodal involvement. Planned re-review of a subset of 202 cases resulted in a change in bone involvement category in 26/202 cases, which was mainly due to difficulty in assessing cortico-medullary junction near the tooth socket and bone fragmentation. The assessment showed moderate to near complete agreement (kappa 0.59-0.82) between 2 observers. Our study shows that bone involvement is not an independent prognostic marker and there is no specific correlation of medullary invasion with outcome over those that showed cortical erosion. Several factors contribute to difficulties and interobserver variability in assessing bone involvement.

A case of langerhans cell histiocytosis accompanying hypothalamus, mastoid bone and liver involvement

A case of langerhans cell histiocytosis accompanying hypothalamus, mastoid bone and liver involvement

Abstract PO5-13-12: Personalized circulating tumor DNA testing for recurrence detection and treatment response monitoring in patients with metastatic invasive lobular carcinoma

Abstract Introduction Metastatic invasive lobular carcinoma (mILC) presents unique challenges during treatment response monitoring. A higher frequency of metastases to the bone, gastrointestinal tract, uterus, meninges, ovary, and diffuse serosal involvement is observed in mILC. The challenge with mILC is that they can be difficult to detect clinically and radiographically, and consequently clinical progression can be difficult to determine with conventional imaging modalities like CT Scans, thus precluding many patients with mILC from enrolling into clinical trials. Therefore more accurate biomarkers are needed to better assess response to treatment in real time. In this study, we demonstrate the feasibility of longitudinal ctDNA testing for treatment response monitoring in patients with mILC. Methods In this real-world study, longitudinal plasma samples (n=219) from 60 patients with mILC, treated across 52 independent clinics between 7/22/21 and 6/15/23, were analyzed. A personalized, tumor-informed ctDNA assay (SignateraTM bespoke, mPCR-NGS assay) was used for detection and quantification of ctDNA in plasma samples. Results In this cohort, the median patient age at diagnosis of metastatic disease (baseline) was 62.9 years (range: 32.2-79.7). Of the 60 patients, 41 (68%) had ER+PR+HER2-, 7 (12%) ER+PR-HER2-, 4 (7%) ER+PR+HER2+, 2 (3%) ER+PR-HER2+, 1 (2%) triple negative breast cancer; receptor status was not available for 5 (8%) patients. CDH1 (75%) and PIK3CA (42%) were observed to be the top two genes with somatic, nonsynonymous mutations. Mutations in TP53 and TBX3 were observed in 13% of patients, mutations in AKAP9, IGFN1, RBM26, and RFC3 in 10% of patients, and mutations in ESR1 in 6.7% of patients. At variant level, PIK3CA p.H1047R (22%) and RBM26 p.Q701Tfs*23 (10%) were the top two somatic variants identified. The most common CDH1 variant, p.Q23*, was found in 5% of the cases. Of the 60 patients, 37 (61.7%) were ctDNA-positive at all time points while on treatment (chemotherapy/endocrine therapy/targeted therapy) with the first time point collected at a median of 6.7 months (range: 2.5-2307 months) from baseline. Of these 37, imaging/biopsy results after baseline were available for 32 patients, 86% (27/32) of whom progressed. Thirty-two of 37 persistently ctDNA-positive patients had serial ctDNA measurements available, of which 14 (43%) had significant increase in ctDNA levels (average: 47-fold increase, standard deviation: 98) from first to last time points. At some point during their care ctDNA was detectable in all (n=51) patients with evidence of clinical progression. Of the 60 patients, 14 (23.3%) were ctDNA-negative at all time points tested. None of the 14 persistently ctDNA-negative patients had evidence of disease recurrence or progression at the time of initial testing or throughout ctDNA monitoring. The first ctDNA time point was collected at a median of 33.1 months (range: 0.68-92 months) from baseline for these patients,a median of 3 time points was tested per patient (1-12). Of the remaining 9/60 patients, 3 (33%) had sustained ctDNA clearance for a median of 46 days (range: 0-224 days) in response to treatment, and 2 (22%) were initially ctDNA-negative but turned positive 105 and 156 days later, indicating potential resistance to treatment and molecular progression. Additional 4/9 (44%) had ctDNA levels consistently low levels (average: 0.42 mean tumor molecules/mL) while on treatment for a median of 260 days (range: 217-442) and showed no evidence of progression. Conclusions ctDNA status and dynamics correlate well with clinical status of patients with mILC, as determined by conventional monitoring tools such as imaging and biopsy. Our results indicate that personalized, tumor-informed, longitudinal ctDNA testing may serve as a useful tool for detection of progression and monitoring treatment response in mILC patients. Citation Format: Steffi Oesterreich, Antony Tin, Samuel Rivero-Hinojosa, Janie Fielder, Jenifer Ferguson, Ekaterina Kalashnikova, Angel Rodriguez, Minetta Liu, Adrian Lee. Personalized circulating tumor DNA testing for recurrence detection and treatment response monitoring in patients with metastatic invasive lobular carcinoma [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 PO5-13-12.

Abstract PO4-15-04: Differential genomic profiling of progesterone receptor (PR) negative, estrogen receptor (ER) positive HER2-negative metastatic breast cancer (MBC) through circulating tumor DNA

Abstract Background: MBC is usually classified based on ER and HER2 status. Although the absence of PR expression is commonly associated with a poorer response to endocrine therapy (ET) and an unfavorable prognosis, data regarding the underlining molecular features that occur in this subgroup are still unclear. The aim of this study was to investigate genomic differences between ER/PRpos HER2neg (PRpos) and ERpos PR/HER2neg (PRneg) MBC through circulating tumor DNA (ctDNA) profiling in a large multicenter consortium. Methods: This retrospective study analyzed a cohort of 1089 patients at Weill Cornell Medicine, Northwestern University, Massachusetts General Hospital, and Washington University in St. Louis with HER2neg MBC and ctDNA testing by Guardant360. Oncogenic pathway status (i.e., RTK, RAS, RAF, MEK, NRF2, ER, WNT, MYC, P53, cell cycle, notch, and PI3K) was defined based on previous research (Sanchez-Vega et al. Cell, 2018). Associations across single nucleotide variations (SNVs), copy number variations (CNVs), pathway classification, and ER/PR status were tested by multinomial logistic regression and corrected for significant clinical characteristics (i.e., lines of treatment, metastatic sites). Prognosis was analyzed through Cox regression for overall survival (OS) defined from time of ctDNA collection. Results: Among the 1089 analyzed patients, PRpos was the most represented subtype (N:580, 53%), followed by PRneg (N:300, 28%) and Triple Negative (TNBC) (N:209, 19%). In the hormone receptor positive subgroup, bone (N:663, 75%), liver (N:323, 37%) and lymph nodes (N:314, 36%) were the main sites of distant involvement. The TNBC group was exposed to significantly fewer lines of therapy (RRR:0.37, P= 0.005 for ≥5 lines). As compared to PRneg, TNBC had less frequent and PRpos had more frequent bone involvement (RRR:0.44, P&amp;lt; 0.001 and RRR:1.80, P&amp;lt; 0.001, respectively) and less frequent liver involvement (RRR:0.64, P=0.019 and RRR:0.71, P=0.020, respectively for TNBC and PRpos). After multivariable analysis, a significant difference with respect to PRneg was observed in SNVs for the PI3K and P53 pathways for TNBC (RRR 0.49 P = 0.013 and RRR 4.06 P &amp;lt; 0.001, respectively) but not for PRpos. On a single gene level, a lower incidence in CDH1 SNVs (RRR 0.09 P = 0.036) and a higher incidence of ESR1 SNVs (RRR 0.09 P = 0.036) was present in PRpos compared to PRneg. TNBC, on the other hand, was characterized by a lower prevalence of KRAS SNVs (RRR 0.09 P = 0.036) and PIK3CA SNVs (RRR 0.25 P &amp;lt; 0.001) and a higher prevalence of TP53 SNVs (RRR 0.09 P &amp;lt; 0.001). No ESR1mutations were detected in TNBC. Median OS was 15 months (mo) for TNBC, 21 mo for PRneg and 31 mo for PRpos (P &amp;lt; 0.001). The differential prognostic impact of ctDNA features on OS was then analyzed across the PRpos and PRneg subpopulations. ESR1 SNVs was prognostic for both subgroups in univariable analysis (HR 2.19 P &amp;lt; 0.001 and HR 1.96 P = 0.001 for PRpos and PRneg, respectively). In multivariable analysis corrected for lines of therapy, ESR1 SNVs retained its significance only in the PRpos subgroup (HR 1.41 P = 0.021) together with NF1 SNVs (HR 2.04 P = 0.034). On the other hand, TP53 SNVs had a significant impact on OS in the PRneg subgroup (HR 2.02 P = 0.014). Conclusions: Our study confirmed the prognostic impact of PR status in ER positive, HER2 negative MBC. Moreover, it suggested a differential profile in terms of ctDNA-detectable genomic features and their impact on survival, including well-established markers such as ESR1 SNVs, with a potential relevance for disease subtyping and future algorithms for drug development trials. Citation Format: Lorenzo Gerratana, Andrew Davis, Arielle Medford, Carolina Reduzzi, Katherine Clifton, Emily Podany, Whitney Hensing, Marko Velimirovic, Ami N. Shah, Lorenzo Foffano, Laura Munoz Arcos, Eleonora Nicolò, Charles S. Dai, Jennifer Keenan, Amir Behdad, Seth Wander, William Gradishar, Cynthia Ma, Fabio Puglisi, Aditya Bardia, Massimo Cristofanilli. Differential genomic profiling of progesterone receptor (PR) negative, estrogen receptor (ER) positive HER2-negative metastatic breast cancer (MBC) through circulating tumor DNA [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 PO4-15-04.

Pediatric Unilateral Chronic Sinusitis: Clinical and Radiological Patterns Compared to Adults.

Upper respiratory tract infections and sinusitis are more prevalent in children than in adults. Unilateral sinusitis is not uncommon disease. Our aim was to analyze the disease characteristics in children with unilateral sinusitis and compare them with those of adults. This study included 124 patients with unilateral chronic sinusitis divided according to age into two groups: pediatric group ≤18 years (66 cases) and adult group >18 years (58 cases). The groups were compared in terms of demographic data, side, clinical manifestations and radiological findings. In pediatric patients, the most common inflammatory pathology was antrochoanal polyps, followed by allergic fungal sinusitis. On the other hand, chronic sinusitis without nasal polyps is the most common in adults, followed by antrochoanal polyps. The mean duration of clinical manifestations before diagnosis in pediatric patients was significantly shorter than that in adults (P=0.001). The most common symptoms in both pediatric and adult patients were anterior nasal discharge and nasal obstruction. Proptosis was significantly higher in pediatric group than in adult group (P=0.015). On computed tomography (CT), the most commonly affected sinus in both pediatric and adult patients was the maxillary sinus followed by the anterior ethmoid sinus. Bone expansion, erosion and involvement of adjacent structures were significantly higher in pediatric patients (P=0.028, 0.027 respectively). Pediatric patients have a high incidence of antrochoanal polyps and allergic fungal sinusitis as unilateral inflammatory lesions. These lesions require surgical management. Inflammatory paranasal sinus lesions in pediatric patients have a shorter duration of clinical manifestations and a higher incidence of bone erosion and involvement of adjacent structures; therefore, early diagnosis and management prevent complications.

The potential advantages of 18F sodium fluoride positron emission tomography-computed tomography for clinical staging and management planning in patients with nasopharyngeal carcinoma.

The staging and treatment planning of nasopharyngeal carcinoma (NPC) face challenges due to limited sensitivity of conventional imaging. 18F-sodium fluoride (18F-NaF) positron emission tomography-computed tomography (PET/CT) offers potential advantages in detecting early bone involvement. This retrospective cohort study aimed to assess the potential advantage of 18F-NaF PET/CT for clinical staging and management planning in patients with NPC and to compare 18F-NaF PET/CT findings with those of conventional imaging modalities. We enrolled a cohort of patients with NPC who underwent 18F-NaF PET/CT at our PET/CT center between July 1, 2017, and June 30, 2021, and analyzed the findings of 18F-NaF PET/CT and conventional imaging modalities. Data from multidisciplinary team discussions on clinical staging and management planning both before and after 18F-NaF PET/CT were recorded. Additionally, any changes in clinical staging and management planning following 18F-NaF PET/CT were documented. A total of 58 patients were included in this study. After 18F-NaF PET/CT imaging, clinical tumor-node-metastasis (TNM) staging was observed to have changed in seven cases (12.1%). Among these, four cases had changes in T stage and three cases in the M stage. Additionally, changes in clinical management plans were observed in eight patients (13.8%). Changes due the results of 18F-NaF PET/CT included three cases with major modification (two cases switched from curative treatment to palliative treatment, and one case switched from palliative treatment to curative treatment) and five cases with minor changes. The minor changes involved alteration to the radiotherapy target volume (three cases with an increased target volume and one case with a reduced target area). Furthermore, one case required an alteration to the radiotherapy strategy for local bone involvement. The use of 18F-NaF PET/CT in patients newly diagnosed with NPC may offer potential advantages for clinical staging and treatment planning, enabling physicians to select a more individualized treatment approach.

Mesenteric panniculitis on 18F-FDG-PET/CT caused by G-CSF therapy mimicking recurrence of lymphoma

We present the case of a 55-year-old woman with Follicular Lymphoma, with basal 18F-FDG-PET/TC showing supra and infradiaphragmatic lymphatic, pleural and bone involvement. Treatment with Epcoritamab + Lenalidomide + Rituximab was iniciated with complete metabolic response (CR). Due to neutropenia, granulocyte colony-stimulating factor (G-CSF) was indicated on 02/22/23 for 5 days. A control PET/CT was performed on 02/23/23 with a pathological increase in metabolism in new-appearing mesenteric soft tissue lesions, suggestive of disease relapse. QT continued without changes and a PET/CT performed on 04/12/23 showed disappearance of the hypermetabolic mesenteric lesions. This suggests that it was a mesenteric panniculitis probably due to the use of G-CSF.

Superficial meningioma with bone involvement: surgical strategies and clinical outcomes.

Meningiomas with bone involvement account for 4.5-17% of all intracranial meningiomas. Little is known about whether these meningiomas (WHO grade I) behave differently than meningiomas without bone involvement. We sought to study the relatively uncommon imaging manifestations of meningioma and to evaluate their clinical significance. A single-institution retrospective cohort study of surgically treated superficial meningioma patients between 2011 and 2022 was conducted. Age, sex, preoperative imaging, operative data, and surgical outcomes were reviewed. Imaging variables and outcomes were reported for patients with bone-invading meningiomas and compared with those with nonbone-invading meningiomas. Univariate analyses were also conducted. Of 577 total superficial meningiomas treated surgically, 47 (8.1%) exhibited bone invasion. Most bone-invading meningiomas were parasagittal (n = 29, 61.7%). A total of 12.7% (n = 6) of patients with bone-invading meningioma had recurrence, whereas 9.1% (n = 48) of patients with non-bone-invading meningioma had recurrence (p = 0.426). No significant difference in the median time to recurrence was observed between patients with bone-invading meningiomas and patients with nonbone-invading meningiomas (69.8 months, Q1:53.1; Q3:81.4 months vs. 69.7 months, Q1:47.5; Q3:96.7; p = 0.638). Superficial meningioma with bone involvement had similar outcomes compared to those of superficial meningioma without bone involvement. Hyperostosis in meningioma (WHO grade I) may not be a surrogate for aggressive meningioma behavior.

A rare case malignant granular cell tumor of the thigh with radiological imaging likely rhabdomyosarcoma: A case report

Granular cell tumors (GCTs) are uncommon soft tissue tumors characterized by the cytoplasmic granular appearance of the neoplastic cells. Malignant GCTs are rare neural tumors, intensely aggressive. Both the rare occurrence of malignant GCTs and its similarities in features with their benign lesions make the diagnosis of this malignancy difficult. Malignant GCTs comprise less than 2% of GCTs and are mostly found in the subcutaneous soft tissues of the lower extremities, especially the thighs. This article presents a case of a large malignant GCTs in the left thigh of a 46-year-old woman. Plain radiograph of the left thigh demonstrated a soft tissue mass without bone involvement. MRI images showed a malignant solid mass 7.8 x 5.2 x 21.6 cm, with ill-defined border, irregular edges, and suspected rhabdomyosarcoma. Incisional biopsy of the mass lesion revealed mixed epithelioid and spindle tumors, suspected malignant GCTs. Histological examination performed by a musculoskeletal pathologist, demonstrated nests and sheets of epithelioid to polygonal cells with hyperchromatic, intensely eosinophilic granular cytoplasm, prominent nucleoli, increased mitotic activity, necrosis, areas of spindling with significant atypia, and positive for S100 by immunohistochemistry. In conclusion, this patient with malignant soft tissue tumor demonstrated polygonal and spindle cells with eosinophilic granular cytoplasm, which need to be considered diagnosed as Malignant GCTs. This case stresses the importance of thorough histological examination in the diagnosis of malignant GCTs.

Complications of Ilizarov method treatment for infected nonunion femoral shaft fracture

Background: Infected non-union of the femur is complicated by the involvement of soft tissue and bone, long-term resistant multi-bacterial infection, limb length discrepancy, deformities, joint stiffness, and multiple draining sinuses, and poses a challenge for orthopedic surgeons. This study aimed to analyze the complications of Ilizarov method treatment for infected non-union femoral shaft fracture. Methods: This prospective observational study was conducted at the national institute of traumatology and orthopedic rehabilitation (NITOR), Dhaka, Bangladesh, from May 2018 to August 2020. A total of 20 patients were selected as study subjects by purposive sampling technique. All data were collected using a pre-formed questionnaire. Data were processed and analyzed using computer software program SPSS version 22.0. Result: The mean bone gap created during the operation was 2.7±1.7 cm of them, in 12 (60%) patients, it was 0 to 2 cm, and in 8 (40%) patients it was more than 2 cm. The mean time needed for radiological union was 7.85±2.1 months ranging from 5 months to 11 months. In 10 (50%) patients, union was achieved within 4 to 7 months, and in 10 (50%) patients it was 8 to 11 months. Regarding limb length discrepancy, in 5 (25%) cases there was no limb length discrepancy (LLD). Twelve patients had 1 cm to 2.4 cm LLD and 3 (15%) patients had ≥2.5 cm LLD. The mean LLD was 1.2±0.9 cm. Regarding complications, in 10 (50%) cases, there was no complication and 10 (50%) patients had complications. The complications were pin tract infection in 7 (35%) patients and wire loosening in 3 (15%) patients. Conclusions: The study concludes that while the Ilizarov ring fixator proves to be a dependable and successful method for stabilizing, correcting length discrepancies, and eliminating infections, it is not without its share of complications. The findings of this research indicate a 50% complication rate among the patients undergoing this treatment.

Perioperative Use of Antibiotics as Infection Prophylaxis in Elective Wrist Arthroscopy: A Nationwide Survey

Wrist arthroscopy is a standard procedure in hand surgery for the diagnosis and treatment of wrist conditions. While perioperative antibiotic prophylaxis (PAP) is not generally recommended for elective hand surgery, there is no official standard for elective wrist arthroscopy. This study aimed to determine the actual clinical use of PAP in elective wrist arthroscopy in Germany and relate it to the structural conditions of clinics performing this procedure. We conducted a systematic search of all facilities in Germany offering wrist arthroscopy. Among these, we performed an online survey using the SoSci Survey online tool via email. PAP is more frequently administered in cases involving simultaneous bone procedures. Cephalosporins are the most commonly used antibiotics in cases of PAP administration. Hospitals administer PAP more frequently than outpatient settings, with most surveyed institutions following facility-specific internal standards for antibiotic administration. The number of arthroscopies performed in the surveyed centres does not influence antibiotic administration. The use of PAP in wrist arthroscopies in Germany is inconsistent. The increased use in arthroscopies with bone involvement corresponds to AWMF guidelines, but a general recommendation for wrist arthroscopies, including soft tissue arthroscopies, is necessary to provide physicians with medical and legal certainty.

Elevated skull fractures: an institutional experience and individual participant data meta-analysis.

Elevated skull fracture (ESF) is a rare but potentially life-threatening type of skull fracture. The literature on this topic is relatively sparse. Herein, we conducted a meta-analysis of all the patients reported in the literature with ESFs with respect to their clinical management to better inform practice. On 20th of January 2023, we conducted a systematic search of literature to find all published cases of ESF. We also conducted a retrospective review of ESF cases from our institution. The data collection and analysis were conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. After screening, 28 studies met the inclusion criteria. A total of 104 individual patients were included in the meta-analysis, with a median age of 24 years and 85.7% of whom were males. 11 patients (11.2%) had an unfavorable outcome while 37 (35.2%) had one or more complications. We found that GCS on admission is an independent predictor of poor outcome in ESF (odds ratio (95% confidence interval) = 1.605 (1.110-2.315), p value = 0.012). Regarding complications, dural injury (odds ratio (95% confidence interval) = 66.667 (7.407-500.00), p value < 0.001) and multiple bone involvement (odds ratio (95% confidence interval) = 6.849 (2.127-22.222), p value = 0.001) were independent predictors of complication. ESFs represent a rare yet consequential form of cranial injury, carrying potentially life-threatening implications if not promptly addressed. In this study, we present the meta-analysis of outcomes and complications within this patient cohort, offering a comprehensive synthesis of existing literature on this pathology. However, further investigation is imperative to provide higher-quality evidence and address lingering uncertainties in the classification and management of ESFs.