Incomplete Surgical Resection Research Articles

Combining single-cell spatial transcriptomics and molecular simulation to develop in vivo probes targeting the perineural invasion region of adenoid cystic carcinoma

Background and objectivesPerineural invasion (PNI) refers to the invasion, encasement, or penetration of tumor cells around or through nerves. Various malignant tumors, including pancreatic cancer, head and neck tumors, and bile duct cancer, exhibit the characteristic of PNI. Particularly, in head and neck-skull base tumors such as adenoid cystic carcinoma (ACC), PNI is a significant factor leading to incomplete surgical resection and postoperative recurrence. MethodsSpatial transcriptomic and single-cell transcriptomic sequencing were conducted on a case of ACC tissue with PNI to identify potential probes targeting PNI. The efficacy of the probes was validated through in vivo and in vitro experiments. ResultsSpatial transcriptomic and single-cell RNA sequencing revealed phenotypic changes in Schwann cells within the PNI region of ACC. Peptide probes were designed based on the antigen-presenting characteristics of Schwann cells in the PNI region, which are dependent on Major Histocompatibility Complex II (MHC-II) molecules. Successful validation in vitro and in vivo experiments confirmed that these probes can label viable Schwann cells in the PNI region, serving as a tool for dynamic in vivo marking of tumor invasion into nerves. ConclusionsPeptide probes targeting Schwann cells' MHC-II molecules have the potential to demonstrate the occurrence of PNI in patients with ACC

Pleural Solitary Tumors - Long-Term Prognosis Related To Surgery And Clinicopathological Criteria.

Pleural solitary fibrous tumors (SFTs) are indolent mesenchymal neoplasias, generally with good prognosis, for which complete surgical resection is the gold standard. However, local recurrences and distant metastases are reported at variable rates. Risk-assessing criteria and models determining recurrence and metastatic risk have been proposed, and can impact on patient follow-up strategies. We conducted an observational study comprising a 12 years period to characterize a cohort of 20 surgically resected thoracic SFTs, and to retrospectively assess the prognostic value of England's histology criteria and Demicco's 4-tier model. All tumors were pleural-based, 12 patients were women, and the mean age at diagnosis was 62.8 years. The median duration of follow-up was ten years, and at the end of the follow-up, all patients were alive, and no distant metastases were reported. Three cases (15%) had local recurrence at the median time of 89.3 months/7.4 years. The only case with an incomplete surgical resection relapsed. Collectively, tumors with worst prognostic features, specifically a positive margin or tumors with malignant histology or non-low-risk features, according to England's and Demicco's models, respectively, were associated with recurrence. These results confirm the importance of complete surgical resection of SFTs, and show that risk stratification criteria and models can predict important surgical outcomes such as recurrence. Moreover, they support a risk-based follow-up schedule, as patients with higher relapse risk can benefit from close follow-up.

Giant Cell Tumor of Soft Tissue: An Updated Review.

Giant cell tumor of soft tissue (GCTST) is a locally aggressive mesenchymal neoplasm of intermediate malignancy that predominantly occurs in the superficial soft tissue of the extremities. It is histologically similar to a giant cell tumor of bone (GCTB) and shows a mixture of round to oval mononuclear cells and osteoclast-like multinucleated giant cells. Currently, immunohistochemistry plays a very limited role in the diagnosis of GCTST. Primary or secondary malignant GCTST has recently been described and tumors exhibiting high-grade histological features demonstrate higher rates of distant metastasis. GCTST lacks the H3-3A gene mutations that are identified in the vast majority of GCTBs, suggesting a different pathogenesis. Surgery is the standard treatment for localized GCTST. Incomplete surgical resection is usually followed by local recurrence. Radiation therapy may be considered when the close proximity of critical structures prevents microscopically negative surgical margins. The systemic treatment options for advanced or metastatic disease are very limited. This review provides an updated overview of the clinicoradiological features, pathogenesis, histopathology, and treatment for GCTST. In addition, we will discuss the differential diagnosis of this peculiar neoplasm.

The impact of time between surgery and adjuvant chemoradiotherapy in advanced oral cavity squamous cell carcinoma.

In advanced oral squamous cell carcinoma (OSCC), adjuvant therapy (AT) is an important part of the treatment to ensure extended locoregional control after primary surgical resection. The impact of the time interval between surgery and AT on the oncological prognosis remains unclear, particularly in high-risk constellations. The aim of this study is to categorize treatment delays and to determine their impact on the oncological prognosis within the context of the histopathological risk parameters of patients with advanced OSCC. In this single-institutional retrospective cohort study, all patients treated for OSCC between 2016 and 2021 and who received postoperative chemoradiation (POCRT) were included. Patients were divided into two groups: Group I: ≤ 6 weeks between surgery and POCRT; and Group II: > 6 weeks between surgery and POCRT. Overall, 202 patients were included (Group I: 156 (77.2%) vs. Group II: 46 (22.8%)). There were no statistically significant differences in epidemiological aspects and histopathological risk factors between the two groups. The maximum time to initiation of POCRT was 11 weeks. Delayed POCRT initiation had no statistically significant influence on the 5-year OS (61.6% vs. 57.3%, p = 0.89), locoregional control rate (38.6% vs. 43.3%, p = 0.57), and RFS (32.3% vs. 30.4%, p = 0.21). On multivariate analysis, extracapsular spread (HR: 2.21, 95% CI: 1.21 - 4.04, p = 0.01) and incomplete surgical resection (HR: 2.01, 95% CI: 1.10 - 3.69, p = 0.02) were significantly correlated with OS. For RFS, ECS (HR: 1.82, 95% CI: 1.15 - 2.86, p = 0.01), incomplete resection (HR: 1.67, 95% CI: 1.04 - 2.71, p = 0.04), and vascular infiltration of the tumor (V-stage; HR: 2.15, 95% CI: 1.08 - 4.27, p = 0.03) were significant risk predictors. Delays in POCRT initiation up to 11 weeks after surgical resection for advanced OSCC were not statistically significantly associated with impaired survival. In cases of prolonged surgical treatment due to management of complications, a small delay in AT beyond the recommended time limit may be justified and AT should still be pursued.

Analysis of 41 cases of non-metastatic Ewing's sarcoma in children

To summarize the clinical characteristics, treatment outcomes, and prognostic factors of children with non-metastatic Ewing's sarcoma (ES). A retrospective analysis was conducted on the clinical data of 41 children with non-metastatic ES diagnosed and treated at the Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine from January 2010 to December 2018. All patients underwent chemotherapy based on the RMS-2009 protocol of the center, and local treatment such as surgery and/or radiotherapy was performed according to risk grouping. The Kaplan-Meier method was used to calculate the overall survival (OS) and event-free survival (EFS) rates. Univariate prognostic analysis was performed using the log-rank test, and multivariate analysis was conducted with Cox regression. Of the 41 children, 21 were male and 20 were female. The median age at diagnosis was 7.7 years (range: 1.2-14.6 years). The median follow-up time for patients with event-free survival was 68.1 months (range: 8.1-151.7 months). As of the last follow-up, 33 patients were in complete remission, and the overall 5-year EFS and OS rates were (78±6)% and (82±6)%, respectively. Univariate analysis by the log-rank test showed that a tumor diameter ≥8 cm, time from diagnosis to start of local treatment ≥16 weeks, and incomplete surgical resection were associated with poor prognosis (P<0.05). Multivariate Cox regression analysis indicated that incomplete surgical resection (HR=8.381, 95%CI: 1.681-41.801, P=0.010) was an independent risk factor for poor prognosis in children with ES. Secondary tumors occurred in 2 cases. A comprehensive treatment strategy incorporating chemotherapy, surgery, and radiotherapy can improve the prognosis of children with ES. Poor prognosis is associated with an initial tumor diameter ≥8 cm, while complete surgical resection and early initiation of local treatment can improve outcomes.

Miniature, multi-dichroic instrument for measuring the concentration of multiple fluorophores.

Identification of tumour margins during resection of the brain is critical for improving the post-operative outcomes. Due to the highly infiltrative nature of glioblastoma multiforme (GBM) and limited intraoperative visualization of the tumour margin, incomplete surgical resection has been observed to occur in up to 80 % of GBM cases, leading to nearly universal tumour recurrence and overall poor prognosis of 14.6 months median survival. This research presents a miniaturized, SiPMT-based optical system for simultaneous measurement of powerful DRS and weak auto-fluorescence for brain tumour detection. The miniaturisation of the optical elements confined the spatial separation of eight select wavelengths into footprint measuring 1.5 × 2 × 16 mm. The small footprint enables this technology to be integrated with existing surgical guidance instruments in the operating room. It's dynamic ability to subtract any background illumination and measure signal intensities across a broad range from pW to mWs make this design much more suitable for clinical environments as compared to spectrometer-based systems with limited dynamic ranges and high integration times. Measurements using optical tissue phantoms containing mixed fluorophores demonstrate correlation coefficients between the fitted response and actual concentration using PLS regression being 0.95, 0.87 and 0.97 for NADH, FAD and PpIX , respectively. These promising results indicate that our proposed miniaturized instrument could serve as an effective alternative in operating rooms, assisting surgeons in identifying brain tumours to achieving positive surgical outcomes for patients.

Investigating the effect of tannin films prepared by low-energy electron beam deposition on the inhibition of bone tumors

Osteosarcoma is a prevalent malignant bone tumor and incomplete surgical resection of the tumor often results in higher rates of local recurrence. To tackle this issue, there is an urgent requirement to develop implants that possess the capability to inhibit tumor recurrence. In this paper, we prepared three different thicknesses of tannin (TA) films on titanium substrates using low-energy electron beam deposition to study their effects on bone tumor inhibition. The structure and morphology of TA films were analyzed by FT-IR, XPS, SEM, and EDX. The release kinetics of tannins were investigated, revealing their ability to achieve sustained release. This sustained release is advantageous for long-term inhibition of bone tumors. Cellular experiments, including cytotoxicity test, live/dead double staining, cell migration and western blot, were performed to evaluate the tumor-suppressing activity of TA films in vitro. The results indicated that the TA films were not only non-cytotoxic to normal bone cells, but also exhibited excellent in vitro anti-tumor activity by effectively inhibiting the activity and migration of bone tumor cells.

Clinical and Pathological Predictors of Death for Adrenocortical Carcinoma.

Adrenocortical carcinoma (ACC) is a rare and lethal disease with a poor prognosis. This study aims to share our 41-year experience as a referral center, focusing on identifying risk factors associated with ACC mortality. Our retrospective analysis included a cohort of 150 adult patients with ACC in all stage categories, treated between 1981 and 2022. Tumor hormonal hypersecretion was observed in 78.6% of the patients, and the median age of diagnosis was 40 years. The majority presented as European Network for the Study of Adrenal Tumors (ENSAT) III or IV (22.9% and 31.2%, respectively), and the overall mortality rate was 54.6%. Independent predictors of death were elevated secretion of cortisol (HR = 2.0), androstenedione (HR = 2.2), estradiol (HR = 2.8), 17-OH progesterone (HR = 2.0), and 11-deoxycortisol (HR = 5.1), higher Weiss (HR = 4.3), modified Weiss (HR = 4.4), and Helsinki scores (HR = 12.0), advanced ENSAT stage (HR = 27.1), larger tumor size (HR = 2.7), higher Ki-67 percentage (HR = 2.3), and incomplete surgical resection (HR = 2.5). Mitosis greater than 5/50 high-power field (HR = 5.6), atypical mitosis (HR = 2.3), confluent necrosis (HR = 15.4), venous invasion (HR = 2.8), and capsular invasion (HR = 2.4) were also identified as independent predictors of death. Knowing the risk factors for ACC's mortality may help determine the best treatment option.

MODL-11. EXPLORING THE THERAPEUTIC POTENTIAL OF YAP-TEAD INHIBITORS FOR TARGETING GBM CELL MIGRATION AT THE INFILTRATIVE MARGIN

Abstract Glioblastoma (GBM) is an aggressive brain tumor with a median overall survival of only 12-15 months. Despite remarkable cellular and molecular heterogeneity, all GBM subtypes exhibit an infiltrating growth pattern which leads to incomplete surgical resection and inevitable recurrence, representing a major obstacle for effective treatment and an unmet need for therapy. Our research project aims to investigate the efficacy of YAP-TEAD inhibitors, including Verteporfin (VP), on migratory properties of GBM cells at the interface between the tumor core and the infiltrative tumor margin. Recently, several groups have implicated Hippo pathway YAP-TEAD activation in GBM growth and mesenchymal transition, and our laboratory demonstrated anti-migration and anti-invasion efficacy of the YAP-TEAD inhibitor VP across GBM subtypes, in patient-derived cell and xenograft (PDX) mouse models. Here we set to develop an ex vivo model for high-throughput testing of various YAP-TEAD inhibitors using organotypic slice cultures obtained from PDX and primary glioblastoma resection specimens, focusing on tumor areas around the infiltrative margin. Tumor cells within 250µ-thick organotypic slices were infected with GFP labeled retrovirus and subjected to confocal time-lapse imaging 72-96 hours later. Slices were treated first with vehicle (DMSO) for 4 hours, and subsequently with the YAP-TEAD inhibitor VP for 4 hours. To assess drug impact on tumor cell migration, we gathered imaging data on migration properties such as speed and directionality. Analysis of a PDX model generated from a de-novo GBM surgical resection (G-17969) revealed significantly decreased distance traveled in GFP+ cells treated with VP, compared to DMSO (p-value = 0.0002, n=50 cells). These pilot results corroborate other studies demonstrating anti-invasion properties of VP, contributing towards our goal of establishing a preclinical pipeline for rapid, high-throughput screening of anti-invasion drug inhibitors ex vivo. Key words: Glioblastoma, cell migration, YAP-TEAD inhibitors, time-lapse imaging

Chimeric Antigen Receptor-T Cell Therapy Decreases Distant Metastasis and Inhibits Local Recurrence Post-surgery in Mice.

Distant metastasis and primary tumor relapse are the two main hurdles to the success of surgical treatment for cancer patients. Circulating tumor cells (CTCs) and incomplete surgical resection are the primary cause of distant metastasis and local recurrence of tumors, respectively. Chimeric antigen receptor (CAR)-modified T cells target residual carcinomas and CTCs hold the potential to inhibit primary recurrence and reduce tumor metastasis, but the experimental evidence is lacking. Here, we developed a surgery-induced tumor metastasis model in immunocompetent mice to investigate the efficacy of CAR-T cells therapy in preventing metastasis and local recurrence. We observed that subcutaneous tumor resection has induced a large number of CTCs intravasated into circulation. EpCAM-specific CAR-T was effective in clearing CTCs following surgical removal of the tumor. This resulted in less pulmonary metastasis and longer survival in mice when compared to mice treated with surgery followed by Mock-T cells infusion. In addition, the local relapse was obviously inhibited at the surgical site followed by EpCAM-CAR-T cell treatment. This study demonstrated that CAR-T cell therapy can be an adjuvant treatment following surgery to prevent tumor metastasis and inhibit primary tumor relapse for cancer patients.

SAT208 Hypercalcemic Crisis In Metastatic Parathyroid Carcinoma: An Unusual Presentation Of A Rare Endocrine Disease

Abstract Disclosure: A. Barnett: None. T. Sliker: None. R.J. Harper: None. G. Elshimy: None. Introduction: Hypercalcemia can be life-threatening with a wide differential, including parathyroid carcinoma (PC), which accounts for only 0.005% of all malignancies in the U.S. Maintaining an index of suspicion for PC in PTH-mediated hypercalcemia is vital for improving long-term survival and outcomes. Frozen section can be misleading when PC is suspected. We describe a case of hypercalcemia due to recurrent metastatic PC 9 years after initial diagnosis. Case: A 57-year-old male presented for endophthalmitis and altered mentation. Records revealed primary hyperparathyroidism with calcium 11.7 mg/dL, PTH 337 (11.1-79.5pg/mL), and 24-hour urine calcium 810 mg/day. Sestamibi showed right lower parathyroid adenoma and a possible right upper parathyroid adenoma. Right superior parathyroidectomy revealed PC invasive into adipose tissue, increased vascularity and positive margins. A hemithyroidectomy and central neck dissection was performed with intraoperative report noting normal-appearing right inferior parathyroid affixed to thyroid, confirmed by frozen section biopsy. The right inferior parathyroid was minced and re-implanted into the right strap muscle. Patient did not return for follow-up. Recent admission labs showed calcium 15.2 mg/dL, ionized calcium 6.8 (4.5-5.3mg/dL), PTH 546 pg/mL, creatinine 1.54 mg/dL, 25-OH vitamin D 21.64 ng/mL, and phosphorus 1.9 mg/dL. He was treated with intravenous fluids, zoledronic acid, and calcitonin. Due to a high suspicion of locally recurrent or metastatic PC, further imaging obtained. A Neck CT and US showed no abnormalities of right surgical bed or cervical lymphadenopathy. Sestamibi revealed a right lower lung lobe nodule, measuring 2.3cm, with intense immediate and delayed uptake concerning for metastatic or primary lung neoplasm and mild focal retention in the right paratracheal region, suspicious for tumor recurrence. PTHrP was negative. He underwent video-assisted thoracoscopic right lower lobectomy that showed an ovoid, well-circumscribed 2.5 x 2.3 x 2.3cm tumor, which stained positive for PAX-8 and synaptophysin, consistent with PC. Discussion: Clinicians should suspect PC in cases with severe hypercalcemia or absolute PTH above 500mg/dL to allow for better surgical planning. Complete en bloc resection is the standard treatment to improve long-term outcomes and reduce disease recurrence. Diagnosis of PC following incomplete surgical resection has increased recurrence rates of greater than 50%. Our patient’s recurrence was 9 years after diagnosis, but most recurrences occur within 2-3 years and occasionally more than 20 years later. The ipsilateral parathyroid was re-implanted based on frozen section results in this patient, which may have been misleading. Frozen sections of parathyroid tissue are notoriously difficult to distinguish normal parathyroid versus PC and only diagnostic in 15% of cases as described in one case series. To reduce the risk of recurrent disease, physicians shouldn’t entirely depend on these results when there is high suspicion for PC. Presentation: Saturday, June 17, 2023

Programming lipopeptide nanotherapeutics for tandem treatment of postsurgical infection and melanoma recurrence

Tumor recurrence and chronic bacterial infection constitute two major criteria in postsurgical intervention for malignant melanoma. One plausible strategy is the equipment of consolidation therapy after surgery, which relies on adjuvants to eliminate the residual tumor cells and inhibit bacterial growth. Until now, a number of proof-of-concept hybrid nanoadjuvants have been proposed to combat tumor recurrence and postsurgical bacterial infection, which may suffer from the potential bio-unsafety or involve complex design and synthesis. The batch-to-batch inconsistencies in drug composition further delay the clinical trials. To circumvent these issues, herein we develop a programmable strategy to generate lipopeptide nanotherapeutics with identical constitution for tandem intervention of postsurgical bacterial infection and cancer recurrence of melanoma. Increasing the number of hydrophobic linoleic acid within lipopeptides has been found to be a simple and practical strategy to improve the therapeutic outcomes for both tumor cells and bacteria. Self-assembled lipopeptide nanotherapeutics with two linoleic acid molecules possesses excellent antitumor activity and antimicrobial function toward both susceptible strains and drug-resistant bacteria. Arising from the incorporation of unsaturated linoleic acid, the unavoidable hemolysis of cationic peptide drugs was effectively alleviated. In vivo therapeutic abilities of postsurgical infection and tumor recurrence were investigated in BALB/c nude mice bearing a B16-F10 tumor model, with an incomplete surgical resection and in situ infection by methicillin-resistant Staphylococcus aureus (MRSA). Self-assembled lipopeptide nanotherapeutics could effectively inhibit cancer cell growth and bacterial infection, as well as promote wound healing. The easily scalable large-scale production, broad-spectrum antitumor and antibacterial bioactivities as well as fixed component endows lipopeptide nanotherapeutics as promising adjuvants for clinically postsurgical therapy of melanoma.

The prognostic power of [11C]methionine PET in IDH-wildtype diffuse gliomas with lower-grade histological features: venturing beyond WHO classification.

IDH-wildtype (IDH-wt) diffuse gliomas with histological features of lower-grade gliomas (LGGs) are rare and heterogeneous primary brain tumours. [11C]Methionine (MET) positron emission tomography (PET) is commonly used to evaluate glial neoplasms at diagnosis. The present study aimed to assess the prognostic value of MET PET in newly diagnosed, treatment naïve IDH-wt gliomas with histological features of LGGs. Patients with a histological diagnosis of IDH-wt LGG who underwent preoperative (< 100days) MET PET/CT and surgery were retrospectively included. Qualitative and semi-quantitative analyses of MET PET images were performed. Progression-free survival (PFS) and overall survival (OS) were analysed by Kaplan-Meier curves. Cox proportional-hazards regression was used to test the association of imaging and clinical data to PFS and OS. We included 48 patients (M:F = 25:23; median age 55). 39 lesions were positive and 9 negative at MET PET. Positive MET PET was significantly associated with shorter median PFS (15.7months vs. not reached, p = 0.0146) and OS time (32.6months vs. not reached, p = 0.0253). Incomplete surgical resection and higher TBRmean values were independent predictors of shorter PFS on multivariate analysis (p < 0.001 for both). Higher tumour grade and incomplete surgical resection were independent predictors of OS at multivariate analysis (p = 0.027 and p = 0.01, respectively). MET PET is useful for the prognostic stratification of patients with IDH-wt glial neoplasms with histological LGGs features. Considering their huge biological heterogeneity, the combination of MET PET and molecular analyses may help to improve the prognostic accuracy in these diffuse gliomas subset and influence therapeutic choices accordingly.

Refractory nonfunctioning pituitary adenomas.

Non-functioning pituitary adenomas (NFPAs) comprise silent tumors of different pituitary lineages that tend to escape early detection and present as invasive macroadenomas with symptoms of mass effect. Incomplete surgical resection is common and may be followed by significant rates of subsequent remnant progression. Pituitary tumors are defined as refractory when resistance to optimal standard therapies including surgery, radiotherapy, and medical treatment is documented. In the absence of approved medications for the treatment of NFPAs, the last criterion to classify these tumors as refractory is ill defined. Silent corticotroph and null cell adenomas have been reported, albeit not in all studies, to be larger and recur more often compared with silent gonadotroph tumors. Nevertheless, it is currently unknown if certain NFPA subtypes are more often refractory using well defined criteria. The response rate to temozolomide is lower in NFPA compared to that seen in functioning tumors. Refractory NFPAs present a significant diagnostic and therapeutic challenge and are associated with increased morbidity and mortality rates.

Performance of 18 F-FAPI PET/CT in assessing glioblastoma before radiotherapy: a pilot study

BackgroundWe aimed to determine the performance of 18 F-FAPI PET/CT used for preprocedural assessment of glioblastoma before radiotherapy.MethodsTwelve glioblastoma patients having undergone incomplete surgical resection or biopsy were examined with 18 F-FAPI PET/CT and MRI scanning before radiotherapy. All patients had confirmed tumor residues according to findings of histopathological and/or long-term clinical and radiological follow-ups. Lesion characterization data, including SUVmax and tumor-to-background ratio (TBR) on PET/CT were attained. PET/CT and MRI findings were compared in terms of number of lesions. The correlation between immunohistochemistry, molecular expression, and PET/CT parameters was also evaluated.Results18 F-FAPI PET/CT detected 16 FAPI-avid out of 23 lesions in 12 patients described on MRI. MRI was statistically different from 18 F-FAPI PET/CT for lesion detection according to the exact McNemar statistical test (P = 0.0156). The SUVmax and TBR of the glioblastomas was 7.08 ± 3.55 and 19.95 ± 13.22, respectively. The sensitivity and positive predictive value (PPV) of 18 F-FAPI PET were 69.6% and 100%, respectively. Neither the Ki-67 index nor the molecular expression was correlated with the FAPI-PET/CT parameters.Conclusion18 F-FAPI PET/CT detects glioblastomas at a lower rate than MRI. However, the 100% PPV of the examination may make it useful for differentiating controversial lesions detected on MRI. The 18 F-FAPI-avid lesions are displayed more clearly probably due to a higher TBR. 18 F-FAPI PET/CT imaging might find application in glioblastoma biopsy and radiotherapy planning.

Role of contrast-enhanced spectral mammography in the assessment of residual disease following neoadjuvant chemotherapy in patients with breast cancer

BackgroundNeoadjuvant chemotherapy (NAC) is currently one of the most commonly utilized treatment options for patients with breast cancer. Evaluating residual disease following NAC is vital in post-chemotherapy treatment planning. Underestimation or overestimation of the residual disease may result in incomplete surgical resection or unnecessary aggressive surgical treatment which can compromise patient survival or result in unwanted morbidity. Contrast-enhanced spectral mammography (CESM) is a new imaging modality that can provide both morphological and anatomical characterization of neoplastic breast lesions when MRI is unavailable or contraindicated. The aim of this prospective observational study was to evaluate the value of CESM in assessing the extent of residual disease following NAC and predicting complete response (CR) with histopathology as the gold standard.ResultsA total of 142 patients were included in our study with invasive duct carcinoma the most prevalent histopathological type seen in 81.7% of cases. The average tumor reduction in size was 40.8% by CESM and 35.8% by histopathology. Comparison between maximum tumor diameter after NAC by CESM and histopathology revealed a high degree of correlation (R = 0.918, p < 0.01). In 45.1% of cases, CESM underestimated the residual tumor size by an average of 1.1 cm. Comparison between CESM and histopathology in predicting CR yielded CESM sensitivity, specificity, positive predictive value (PPV), and negative predictive values (NPV) of 96.7%, 84.6%, 97.2%, and 100%, respectively.ConclusionsCESM is a new effective imaging modality in assessing residual disease in breast cancer patients receiving NAC. Post-NAC CESM correlated well with residual tumor size by histopathology with a tendency for underestimation. Careful assessment of CESM images should be made to accurately measure the exact tumor size to avoid overestimation or underestimation potentially increasing the extent of the operation. Proper assessment of the true extent of residual disease can help the surgeon to select the optimal surgical technique ensuring radical treatment of the disease improving patient survival and reducing morbidity.

GAB1 as a Marker of Recurrence in Anterior Skull Base Meningioma.

About one-third of anterior skull base meningiomas show Hedgehog pathway activation. We have recently identified GAB1 as a surrogate marker for Hedgehog pathway-activated meningiomas. To determine the reproducibility and prognostic value of GAB1 marker in anterior skull base meningiomas. A retrospective bicentric cohort of anterior skull base meningiomas, operated from 2005 to 2015, was constituted. GAB1 immunohistochemistry was performed in 2 centers, and the GAB1 score was assessed. Clinical and pathological data were reviewed to determine the prognostic value of the GAB1 score, along with classical factors of recurrence. One hundred forty-eight patients were included (median follow-up of 72 ± 46 months). 78% of patients had gross total resection. Eighty-four percentage of patients harbored grade 1 meningiomas. GAB1 immunohistochemistry was positive (ie, GAB1 staining score was >250) in 53 cases (35%). GAB1-positive cases were mainly at olfactory groove, of meningothelial grade 1 subtype, and showed greater recurrence (36% vs 14%, P = .002), greater requirement for multiple surgeries (17% vs 4.2%, P = .014), and more likely evolution toward diffuse skull base infiltration (15% vs 3%, P = .0017). By multivariable Cox regression analysis, incomplete surgical resection (hazard ratios [HR] = 8.3, 95% IC [3.7-18.2], P < .001), male sex (HR = 5.4, 95% IC [2.2-13.5], P < .001), GAB1 positivity (HR = 3.2, 95% CI [1.5-6.9], P = .004), and Ki67 index >4 (HR = 2.2, 95% IC [1.2-4.6], P = .035) were independent prognostic factors for recurrence. GAB1 marker is an independent prognostic factor for anterior skull base meningioma and could be useful for both prognostic evaluation and identification of Hedgehog-activated meningiomas.

The Effect of the Time Interval between Temozolomide and Radiotherapy in Adjuvant High-Grade Glioma Treatment

<h3>Purpose/Objective(s)</h3> The standard of care for high grade glioma (HGG) treatment consists of postoperative radiotherapy and temozolamide (TMZ). The effect of time between TMZ administration and RT on treatment outcomes is not well defined. The purpose of this study was to examine the interval between oral administration of TMZ and RT, and its effect on treatment outcomes in patients with HGG. <h3>Materials/Methods</h3> The clinical data of 277 patients with HGG treated between 2009 – 2021 at four centers were retrospectively analyzed. The following are the inclusion criteria: Pathologically proven grade ≥3 glial tumors, ≥18 years old, and completion of curative RT with concurrent oral 75 mg/m²/day TMZ. Patients who were unable to take oral TMZ, or had previously been treated with TMZ and/or RT were excluded. The TMZ to RT interval (TRI) was calculated from the time of oral TMZ administration to the time of RT fraction. In relation to the TMZ half-life, the interval time was divided into <2 h and ≥2 h groups. Progression free survival (PFS) is calculated as the time between the end of RT and clinical or radiological progression. Overall survival (OS) is calculated from the time of diagnosis to the last follow-up. <h3>Results</h3> The median age was 58 years (range: 19–81). 159 patients (57.4%) were male, while 118 (42.6%) were female. 75.4% of patients had an ECOG performance score (ECOG PS) of 0–1, and 54.5% had gross total resection (GTR). The median fraction and total RT doses were 2 Gy (1.8–3) and 60 Gy (40–60), respectively. The median follow-up was 15.2 months (range: 1.9–75.1) for the entire cohort. Two-year OS and PFS rates were 35% and 15%, respectively. After completion of RT, disease progression occurred in 255 patients (92.1%) at a median of 6.4 months (range, 0.2–64.9). The 2-year OS was 42.8% for patients with a TRI >2 hours and 32% for patients with a time interval of ≤2 hours (p = 0.18). Similarly, there was no statistically significant difference in 2-year PFS between the two groups (12.8% vs. 9%; p = 0.95). Age, ECOG PS, and type of surgery were all significant prognostic factors for OS and PFS in univariate analysis. In multivariate analysis, advanced age [HR = 1.03 (95% CI, 1.01 – 1.04); p<0.001], poor ECOG PS [HR = 2.14 (95% CI, 1.56 – 2.94); p<0.001], and incomplete surgical resection [HR = 1.39 (95% CI, 1.06–1.84); p = 0.02] were independent predictors of poorer OS. Similarly, age [HR = 1.02 (95% CI, 1.01 – 1.03); p = 0.002], ECOG PS [HR = 1.57 (95% CI, 1.17 – 2.09); p = 0.002], and type of surgery [HR = 1.41 (95% CI, 1.10 – 1.80); p = 0.006] were all significant prognostic factors for PFS in multivariate analysis. <h3>Conclusion</h3> We found that advanced age, poor performance status, and incomplete surgical resection were all predictive of poor OS and PFS in this current study. However, we were unable to detect a statistically significant effect of the time interval between oral administration of TMZ and RT. Validation of our findings will require a longer follow-up period and randomized trials.

Prognostic Ability of Tumor Budding Outperforms Poorly Differentiated Clusters in Gastric Cancer.

Simple SummarySmall clusters of tumor cells at the invasion front of the tumor, known as “tumor budding” and larger clusters of cells, known as “poorly differentiated clusters”, are well known histological parameters to assess the outcome of colorectal cancer. However, their prognostic value for gastric cancer is less well investigated and controversial based on the studies conducted so far. In our retrospective study, we investigated the prognostic power of these two entities in a large cohort of gastric cancer patients. Our results demonstrate that tumor budding is an independent prognostic factor determining overall survival in gastric cancer, especially in intestinal type adenocarcinomas. In addition, budding can also predict the risk of lymph node metastases. However, although the trend is similar for poorly differentiated clusters, their predictive value is lower and they have not been shown to be an independent prognostic factor of survival in gastric cancer.The prognostic value of histological phenomena tumor budding (TB) and poorly differentiated clusters (PDCs) have been less studied in gastric cancer (GAC) and the data provided so far are controversial. In our study, 290 surgically resected GAC cases were evaluated for TB according to the criteria of International Tumor Budding Consensus Conference (ITBCC) and PDC, and both parameters were scored on a three-grade scale as described for colorectal cancer previously (0: Grade0, 1–4: Grade1, 5–9: Grade2 and ≥10: Grade3) and classified as low (Grade0–2) and high (Grade3) TB/PDC. High TB/PDC was associated with diffuse-type morphology, higher pT status, incomplete surgical resection, poor tumor differentiation and perineural and lymphovascular invasion. Multivariable survival analyses have shown an independent prognostic role of high TB with poorer overall survival in the total cohort (p = 0.014) and in intestinal-type adenocarcinomas (p = 0.005). Multivariable model revealed high TB as an independent predictor for lymph node metastasis in both the total cohort (p = 0.019) and in the intestinal type adenocarcinomas (p = 0.038). In contrast to tumor budding, no significant association was found between PDC and the occurrence of lymph node metastasis and tumor stage and even survival. In conclusion, tumor budding is an independent prognostic factor of survival in gastric cancer, especially in intestinal-type adenocarcinomas.

M1.2 Human pythiosis

Meet the expert session, September 22, 2022, 8:00 AM - 9:00 AMHuman pythiosis is a rare, life-threatening infection, which is generally caused by Pythium insidiosum, a fungal-like oomycete. Four forms of human pythiosis are described: 1) vascular pythiosis affecting the patient's arteries causing arteritis, thrombosis, and gangrene; 2) ocular pythiosis, mainly causing infections of the cornea; 3) skin and soft tissue infections (cutaneous and subcutaneous pythiosis); and 4) disseminated pythiosis. Vascular pythiosis is associated with high morbidity and has a mortality rate of 10%-40%, which attributes to difficulties in diagnosis of the infection and the lack of effective standard treatment. Rice farmers and patients with thalassemia are at risk for vascular infection. Early diagnosis of Pythium infection requires a high index of clinical suspicion and is essential for good treatment results. Microscopic morphology of Pythium spp. resembles other non-septate hyphae, such as agents of mucormycosis. Definite laboratory diagnosis includes tissue cultivation with zoospore induction, polymerase chain reaction (PCR), and detection of Pythium antibodies. Radical surgery together with immunotherapy, and anti-fungal agents (e.g., terbinafine and itraconazole) have previously been used for the treatment of human pythiosis. However, patients with incomplete surgical resection had almost 100% mortality. A novel therapeutic approach and reliable biomarkers are needed to improve patient outcomes. There are several studies demonstrating excellent in vitro activity of antibacterial agents, especially macrolides, tetracyclines, and oxazolidinone against P. insidiosum. There are also evidences of synergy among antibacterial classes such as tetracyclines and macrolides. In 2019, Susaengrat, et al. reported successful treatment of two patients, who had inoperable intra-abdominal vascular pythiosis, with adjunctive antibacterial agents as salvage therapy. The medications included itraconazole in combination with doxycycline and azithromycin or clarithromycin. This case report also confirmed the result of a previous study by Worasilchai, et al. (2018) that serum 1,3-beta-D-glucan (BDG) is useful for monitoring disease activity. The ongoing multicenter prospective study is conducted to evaluate the use of antibacterial agents (azithromycin and doxycycline) with itraconazole and surgery in vascular pythiosis and to evaluate the alternative markers such as erythrocyte sedimentation rate (ESR) and c-reactive protein (CRP). Torvorapanit, et al. (2021) reported preliminary results of 10 patients, which demonstrated favorable outcomes. It was shown that 2/4 patients with the residual disease could successfully be treated with mediations. ESR and CRP declined over time after treatment and Spearman's correlation between ESR and BDG was 0.65, and between CRP and BDG was 0.6. The study aims to recruit 50 patients, which should attest the usefulness of antibacterial agents and these markers in patients with vascular pythiosis.