Significant Tumor Research Articles

Monolayer-fluorescence counting for ultrasensitive detection of tumour cell-derived extracellular vesicles using a step-wedge microfluidic platform

Extracellular vesicles have emerged as significant noninvasive tumour biomarkers, and ultrasensitive detection methods are important for early cancer diagnosis. Here, a monolayer-fluorescence counting strategy was developed for the ultrasensitive detection of extracellular vesicles using a microfluidic platform. Extracellular vesicles were specially captured and separated from complex matrix by immune magnetic microbeads (IMBs). With an enhancing acoustic wave microfluidic channel, the magnetic-extracellular vesicles immune complex was adequately mixed and reacted with antibody-modified fluorescence microbeads (IFBs). Using a newly designed step-wedge microfluidic structure, micrometer-size particles were trapped in large numbers with monolayer in the step zone, and the fluidic resistance was reduced through the wedge structure. This detection signal of the fluorescence-labelled immune sandwich complex could be read by counting, avoiding background interference and achieving an ultrasensitive detection with a detection limit of 850 particles/mL. Moreover, this method showed strong reliability and specificity in clinic samples. In addition, a miniaturized detection device was developed based on this microfluidic platform, improving this detection automation.

Mesoporous polydopamine (MPDA)-based drug delivery system for oral chemo-photothermal combinational therapy of orthotopic colon cancer

Oral nano-drug delivery systems offering combination therapy have garnered significant interest in colon cancer treatment due to their precision in targeting tumors and minimizing peripheral tissue exposure. However, challenges such as the complex gastrointestinal environment and effective retention of nanoparticles in the colon have impeded further advancement. We developed a novel oral drug delivery system designed for localized treatment of colon cancer via chemotherapy and photothermal therapy (PTT). This system utilized mesoporous polydopamine (MPDA) as a photothermal carrier for doxorubicin hydrochloride (DOX), with surface modification using folic acid (FA) to enhance systemic tumor targeting. Additionally, to ensure gastrointestinal retention and precise colon localization, the nanoparticles were coated with an enteric-soluble material, ES100, resulting in the formulation MPDA-FA-DOX/ES100. This formulation exhibited high photothermal conversion efficiency, robust photothermal stability, and responsive drug release under near-infrared (NIR) laser stimulation. FA modification significantly enhanced the cellular uptake of nanoparticles by CT26 cells, promoting greater cytotoxic effects through combined chemotherapy and PTT. In vivo, MPDA-FA-DOX/ES100 demonstrated superior accumulation in colon tumor tissues and substantial photothermal effects, and notably, the CT/PTT group demonstrated significant tumor growth inhibition along with excellent biocompatibility. Collectively, these findings highlight the clinical potential of MPDA-FA-DOX/ES100 as an effective platform for localized and synergistic CT/PTT of colon cancer.

Dual-emission carbon dots-based biosensor for polarity/targeting bimodal recognition and mild photothermal therapy of tumor

It is essential to develop a multifunctional nanoplatform for biosensing, tumor diagnosis and treatment simultaneously. Herein, dual-emission fluorescent carbon dots (HA-CDs) were fabricated via a one-pot solvothermal method using spinach powder as carbon source and hyaluronic acid (HA) as targeting agent. The obtained HA-CDs exhibited outstanding optical properties, good targeted tumor and excellent photothermal conversion performance. Interestingly, HA-CDs can sensitively perceive the changes in polar environments attributed to the inherent ratiometric fluorescence characteristics, and combined with the intrinsic targeting tumor ability achieved tumor cell recognition. More importantly, the HA-CDs possess good photothermal conversion efficiency of 21.2 % to be beneficial for photothermal therapy of tumors. The survival rate of HeLa cells incubated with HA-CDs dramatically decreased to 14 % after 660 nm laser irradiation, revealing the significant tumor inhibition of HA-CDs in vitro. Notably, through individual intraperitoneal and intratumoral injection, it was found that HA-CDs demonstrated a similar tumor suppressed effect on 4T1 tumor-bearing mice exposed to laser irradiation, fully uncovering that HA-CDs can efficiently accumulate at tumor site by intraperitoneal injection. Besides, the histopathological analysis of major organs ex vivo revealed a good biosafety profile. Collectively, this strategy of designed HA-CDs provides a new multifunctional nanoplatform for potential clinical application.

Clinical experiences in precision treatment of giant plexiform neurofibromas of head, face, and neck

To summarize the treatment strategies and clinical experiences of 5 cases of giant plexiform neurofibromas (PNF) involving the head, face, and neck. Between April 2021 and May 2023, 5 patients with giant PNFs involving the head, face, and neck were treated, including 1 male and 4 females, aged 6-54 years (mean, 22.4 years). All tumors showed progressive enlargement, involving multiple regions such as the maxillofacial area, ear, and neck, significantly impacting facial appearance. Among them, 3 cases involved tumor infiltration into deep tissues, affecting development, while 4 cases were accompanied by hearing loss. Imaging studies revealed that all 5 tumors predominantly exhibited an invasive growth pattern, in which 2 and 1 also presenting superficial and displacing pattern, respectively. The surgical procedure followed a step-by-step precision treatment strategy based on aesthetic units, rather than simply aiming for maximal tumor resection in a single operation. Routine preoperative embolization of the tumor-feeding vessels was performed to reduce bleeding risk, followed by tumor resection combined with reconstructive surgery. All 5 patients underwent 1-3 preoperative embolization procedures, with no intraoperative hemorrhagic complications reported. Four patients required intraoperative blood transfusion. A total of 10 surgical procedures were performed across the 5 patients. One patient experienced early postoperative flap margin necrosis due to ligation for hemostasis; however, the incisions in the remaining patients healed without complications. All patients were followed up for a period ranging from 6 to 36 months, with a mean follow-up duration of 21.6 months. No significant tumor recurrence was observed during the follow-up period. For patients with giant PNF involving the head, face, and neck, precision treatment strategy can effectively control surgical risks and improve the standard of aesthetic reconstruction. This approach enhances overall treatment outcomes by minimizing complications and optimizing functional and cosmetic results.

Single-cell and spatial transcriptome characterize coinhibitory cell-cell communications during histological progression of lung adenocarcinoma.

Lung adenocarcinoma, a prevalent and lethal malignancy globally, is characterized by significant tumor heterogeneity and a complex tumor immune microenvironment during its histologic pattern progression. Understanding the intricate interplay between tumor and immune cells is of paramount importance as it could potentially pave the way for the development of effective therapeutic strategies for lung adenocarcinoma. In this study, we run comparative analysis of the single-cell transcriptomic data derived from tumor tissues exhibiting four distinct histologic patterns, lepidic, papillary, acinar and solid, in lung adenocarcinoma. Furthermore, we conducted immunofluorescence assay and spatial transcriptomic sequencing to validated the spatial co-localization of typical co-inhibitory factors. Our analysis unveiled several co-inhibitory receptor-ligand interactions, including PD1-PDL1, PVR-TIGIT and TIGIT-NECTIN2, that potentially exert a pivotal role in recruiting immunosuppressive cells such as M2 macrophages and Tregs into LUAD tumor, thereby establishing immunosuppressive microenvironment and inducing T cells to exhaustion state. Furthermore, The expression level of these co-inhibitory factors, such as NECTIN2 and PVR, were strongly correlated with low immune infiltration, unfavorable patient clinical outcomes and limited efficacy of immunotherapy. We believe this study provides valuable insights into the heterogeneity of molecular, cellular interactions leading to immunosuppressive microenvironment during the histological progression of lung adenocarcinoma. The findings could facilitate the development of novel immunotherapy for lung cancer.

CapeOX as neoadjuvant chemotherapy for locally advanced rectal cancer: might less be more?

BackgroundLocally advanced rectal cancer (LARC) poses unique challenges in treatment, with current neoadjuvant chemoradiotherapy (NA-CRT) showing limitations. The CapeOX regimen emerges as a potential less aggressive neoadjuvant chemotherapy (NAC) for LARC.MethodsWe conducted a retrospective study involving treatment-naïve patients with LARC from March 2014 to March 2021 who received 2–4 cycles of CapeOX NAC followed by radical surgery. Treatment response was evaluated using tumor regression grade (TRG), MRI-based TRG (MRI-TRG), and Neoadjuvant Rectal (NAR) score.Results94.7% of patients experienced symptom improvement and 96.4% achieved sphincter-preserving surgery. Post-NAC showed significant tumor regression and MRI confirmed a tumor length reduction (P < 0.001). Clinical and pathological staging discrepancies post-NAC suggest broader therapeutic advantages. 5-year overall and disease-free survival rates were 78.4% and 73.4%. NAR scores provided better prognostic accuracy than MRI-TRG.ConclusionCapeOX NAC presents notable benefits for LARC patients and its clinical significance may be underestimated. The NAR score demonstrates superior prognostic value over MRI-TRG.

The efficacy of different biomarkers and endpoints to refine referrals for suspected prostate cancer: the TARGET study (Tiered integrAted tests for eaRly diaGnosis of clinically significant ProstatE Tumours).

The majority of men referred with a raised PSA for suspected prostate cancer will receive unnecessary tertiary investigations including MRI and biopsy. Here, we compared different types of biomarkers to refine tertiary referrals and when different definitions of clinically significant cancer were used. Data and samples from 798 men referred for a raised PSA (≥ 3ng/mL) and investigated through an MRI-guided biopsy pathway were accessed for this study. Bloods were acquired pre-biopsy for liquid biomarkers and germline DNA. Variables explored included PSA + Age (base model), free/total PSA (FTPSA), Prostate Health Index (phi), PSA density (PSAd), polygenic risk score (PRS) and MRI (≥ LIKERT 3). Different diagnostic endpoints for significant cancer (≥ grade group 2 [GG2], ≥ GG3, ≥ Cambridge Prognostic Group 2 [CPG2], ≥ CPG3) were tested. The added value of each biomarker to the base model was evaluated using logisticregression models, AUC and decision curve analysis (DCA) plots. The median age and PSA was 65years and 7.13ng/mL respectively. Depending on definition of clinical significance, ≥ grade group 2 (GG2) was detected in 57.0% (455/798), ≥ GG3 in 27.5% (220/798), ≥ CPG2 in 61.6% (492/798) and ≥ CPG3 in 42.6% (340/798). In the pre-MRI context, the PSA + Age (base model) AUC for prediction of ≥ GG2, ≥ GG3, ≥ CPG2 and ≥ CPG3 was 0.66, 0.68, 0.70 and 0.75 respectively. Adding phi and PSAd to base model improved performance across all diagnostic endpoints but was notably better when the composite CPG prognostic score was used: AUC 0.82, 0.82, 0.83, 0.82 and AUC 0.74, 0.73, 0.79, 0.79 respectively. In contrast, neither FTPSA or PRS scores improved performance especially in detection of ≥ GG3 and ≥ CPG3 disease. Combining biomarkers did not alter results. Models using phi and PSAd post-MRI also improved performances but again benefit varied with diagnostic endpoint. In DCA analysis, models which incorporated PSAd and phi in particular were effective at reducing use of MRI and/or biopsies especially for ≥ CPG3 disease. Incorporating phi or PSAd can refine and tier who is referred for tertiary imaging and/or biopsy after a raisedPSA test. Incremental value however varied depending on the definition of clinical significance and was particularly useful when composite prognostic endpoints are used.

Vimseltinib versus a placebo in patients with tenosynovial giant cell tumor: a plain language summary of the MOTION phase 3 trial.

This article presents a patient-friendly summary of the MOTION phase 3 clinical trial results, which were published in The Lancet in June 2024.The primary goal of the MOTION trial was to understand if treatment with a drug called vimseltinib shrank tumors more than a placebo in participants with symptomatic tenosynovial giant cell tumor, also known as TGCT, for which surgery was unlikely to provide benefit. A placebo is something that looks like the treatment being studied but does not contain any medicine.The MOTION trial compared the effects of vimseltinib versus a placebo using several different outcomes associated with TGCT. These outcomes included tumor size, active range of motion of the affected joint, and several patient-reported quality-of-life measures including physical function, stiffness, overall health, and pain. The trial showed that more participants treated with vimseltinib experienced significant tumor shrinkage, as defined by a 30% or greater reduction in tumor size, compared with those receiving a placebo. Participants receiving vimseltinib had improved active range of motion, and they reported improved physical function, stiffness, overall health, and pain, regardless of the amount of tumor shrinkage, compared with participants receiving a placebo. Most side effects in participants treated with vimseltinib were not severe and were manageable. Vimseltinib was better at shrinking tumors and improving active range of motion, stiffness, pain, and other health measures than the placebo for participants with TGCT. Vimseltinib has the potential to become a new treatment option for patients with TGCT for whom surgery may not provide benefit.

Enhanced Oncolytic Potential of Engineered Newcastle Disease Virus Lasota Strain through Modification of Its F Protein Cleavage Site.

Newcastle disease virus (NDV) is an oncolytic virus whose F protein cleavage activity is associated with viral infectivity. To explore the potential of modifying F protein cleavage activity to enhance antitumor effects, we constructed a recombinant NDV LaSota strain by replacing its F protein cleavage site with that from the mesogenic Beaudette C (BC) strain using reverse genetics techniques. The resulting virus, rLaSota-BC-RFP, demonstrated significantly enhanced infectivity and tumor cell suppression on the murine melanoma B16F10 cell, characterized by higher cytotoxicity and increased apoptosis compared to its parental strain, rLaSota-RFP. In vivo, rLaSota-BC-RFP treatment of B16F10 tumors in C57BL/6 mice resulted in significant tumor growth inhibition, improved survival rate, and induction of tumor-specific apoptosis and necrosis. Additionally, the rLaSota-BC-RFP treatment enhanced immunostimulatory effects within the tumor microenvironment (TME), characterized by increased infiltration of CD4+ and CD8+ T cells and elevated levels of antitumor immune modulator cytokines, including mouse IL-12, IFN-γ, IL-15, and TNF-α, in the rLaSota-BC-RFP-treated tumor tissues. Collectively, these findings demonstrate that the mesogenic F protein cleavage site enhances the oncolytic potential of the NDV LaSota strain, suggesting that rLaSota-BC-RFP is a promising oncolytic viral vector for gene delivery in cancer immunotherapy.

8172 Retrospective Analysis of mRNA Expression Based Signatures of Thyroid Tumor Invasion and Metastases

Abstract Disclosure: S. Ahmadi: None. E. Namiranian: None. M. Alshalalfa: Employee; Self; Veracyte, Inc.. Stock Owner; Self; Veracyte, Inc. R. Jiang: Employee; Self; Veracyte, Inc.. Stock Owner; Self; Veracyte, Inc. Y. Hao: Employee; Self; Veracyte, Inc.. Stock Owner; Self; Veracyte, Inc. J.P. Klopper: Employee; Self; Veracyte, Inc.. Stock Owner; Self; Veracyte, Inc. R.T. kloos: Employee; Self; Veracyte, Inc.. Stock Owner; Self; Veracyte, Inc.. E. Marqusee: None. The American Thyroid Association thyroid cancer risk stratification system is driven primarily by the extent of vascular and extrathyroidal extension, as well as lymph node metastases. Minimizing surgical intervention for thyroid tumors from indeterminate thyroid nodules (ITN - Bethesda III and IV cytology) is often preferred to mitigate surgical complications and lessen the need for thyroid hormone supplementation post-operatively if clinical outcomes are not worsened. By leveraging the whole transcriptome derived Afirma Genomic Sequencing Classifier (GSC) thyroid nodule molecular testing platform, mRNA expression-based signatures were developed to predict thyroid tumors with a low risk of clinically significant invasion and metastases with a &amp;gt; 95% negative predictive value as part of the Afirma Genomics Resource for Intelligent Discovery (GRID). The objective of this study was to analyze the performance of these signatures on a retrospective cohort of patients with ITN who had Afirma GSC suspicious findings and thyroid surgery. Two hundred three subjects were evaluated, and pathology reports were scored for the extent of thyroid tumor invasion or metastases. Tumors with extensive vascular invasion or extrathyroidal extension are labeled as high risk (and otherwise are low risk). Tumors with lymph node metastases that either have documented &amp;gt; 2mm tumor deposits, &amp;gt; 40% of central nodes involved, or lateral lymph node metastases are labeled as high risk (and otherwise are low risk). The Afirma GRID invasion and metastases signatures were applied to correlate with the pathology scoring. The cohort was comprised of 144 (70%) female and 59 (30%) male patients with median age of 54 [IQR 40-65]. The cohort was mostly Bethesda III (n= 152, 75%). Fifty three percent (n=109) of the samples were malignant upon histology review. Two samples were scored as high risk for lymph node metastases (LNM) and 4 samples were scored as high risk for invasion (INV) based on final pathology. The LNM signature ruled out 55% of samples with 100% NPV and 55% specificity. No samples with high risk LNM scores were erroneously ruled out by the LNM GRID signature. The rule out % was similar in female (58%) and males (46%) (chi-squared test p=0.1). For the invasion model, 57% of samples were ruled out with 99% NPV and 57% specificity. One sample with extra-thyroidal invasion had a false negative GRID INV signature. The INV rule out % was similar in female (57%) and males (54%) (chi-squared test p=0.19). In summary, the Afirma GRID INV and LNM signatures ruled out clinically significant thyroid tumor features in &amp;gt; 50% of the studied cohort with &amp;gt; 95% NPV. Prospective studies should be performed to confirm the potential for Afirma GRID tumor behavior signatures to optimize and individualize surgical decision-making, decreasing the burden of unnecessary extent of thyroid surgery while maintaining outstanding clinical outcomes. Presentation: 6/3/2024

7428 Clinical and Radiological Characterization and Outcomes of Lipid-Poor Adrenal Masses- A Multi-Center Retrospective Study

Abstract Disclosure: V. Balderrama-Brondani: None. R. Al-ward: None. K. Kiseljak-Vassiliades: None. L.M. Fishbein: None. D.A. Kirelik: None. O. Hamidi: None. R. Pishdad: None. H.K. Ghayee: None. M. Sukkari: None. S.S. Bedrose: None. A.H. Hamrahian: None. M.A. Habra: None. Background: Lipid-poor adrenal masses (LPAMs) with pre-contrast radiodensity &amp;gt;10 Hounsfield Units (HU) on computed tomography (CT) represent ∼25% of adrenal tumors. There is limited data about the natural history of LPAMs; therefore, we evaluated a large series of patients with LPAMs to describe the radiological and clinical features and outcomes of these cases. Methods: We conducted a multi-center retrospective cohort study of patients with LPAMs with a baseline diameter of 10-39 mm and derived from 6 institution members of the American-Australian-Asian Adrenal Alliance (A5). We excluded suspected or proven adrenal metastasis, pheochromocytoma, sarcoma, lymphoma, myelolipoma, infiltrative lesions, and adrenal hemorrhage, as well as patients with personal/familial history of genetic predisposition to adrenal neoplasms. The data is presented in percentage and median (range). Results: A total of 242 adrenal masses from 218 patients were evaluated, but only 225 (93%) masses met the inclusion criteria and were analyzed. The age was 58 (23-92), and 61% were women. LPAMs were incidentally discovered in 155 (71.1%) cases, 32 (14.7%) cases were diagnosed due to hormonal overproduction, and 17 (7.8%) due to pain/mass effect. Forty-six (21.1%) patients were on surveillance for a history of extra adrenal malignancy. Masses were unilateral in 89.9% (left side, 57.1%), with size 21 (10-38) mm, with a pre-contrast density of 24 (11-136) HU. Absolute washout was reported in 107 LPAMs and was &amp;gt;60% in 73 (68.2%) cases. The follow-up time was 44.4 (0.9-241) months. Hormonal overproduction developed during the follow-up in 23 (10.5%) cases as follows: cortisol in 15 (6.9%), aldosterone in 4 (1.8%), and sex hormones in 3 (1.4%) cases. LPAM growth rate was 0.03 (-2.18-11.59) cm/year. Seventy-one masses (31.5%) underwent diagnostic procedures (surgery/biopsy) with adrenocortical adenoma (n=37; 52.1%) and adrenocortical carcinoma (ACC) (n=25; 35.2%) being the two most common diagnoses. The tumor growth rate of pathologically confirmed adenomas was 0.03 (-0.30-10.50) cm/year, and of ACC was 1.31 (0.03-11.59) cm/year. A total of 154 (68.4%) LPAMs remained under surveillance at the end of the study, with a follow-up time of 51.8 (6-241) months and a tumor growth rate of 0.02 (-2.18-1.36) cm/year. Forty-five (20.6%) LPAMs decreased by 2 mm (1-13) during the study period. Cases that proved to be ACC had the most significant tumor growth rate over the study (p&amp;lt;0.001). The median time between the initial discovery of LPAM and the surgical resection of ACC cases was 34 (6-128) months. Conclusion: Our study showed that LPAMs carry significant malignant potential, and close long-term follow-up is warranted when surgical resection is not pursued. Prospective studies are critically needed to validate our findings and to establish high-risk molecular, imaging, and biochemical features associated with malignancy. Presentation: 6/2/2024

12612 Chiasmal Herniation - A Rare Complication Of Prolactinoma Treatment

Abstract Disclosure: A. Syeda: None. V. Kantorovich: None. Introduction: Primary treatment of symptomatic prolactinomas is medical therapy with dopamine agonists (DA). Herniation of optic chiasm is a rare complication of tumor shrinkage induced by DA therapy which causes secondary deterioration in visual fields. Case:A 26-year-old man presented to our hospital after a syncopal episode. He had headaches and blurry vision in the left eye for the past 4 months. He was diagnosed with a 4 cm x 3.6 cm x 2.6 cm pituitary macroprolactinoma compressing the optic chiasm, his prolactin (PRL) was 4700 ng/mL (N: 4.0-15.2 ng/mL) and testosterone was suppressed to 10 ng/dL (N: 249-836 ng/dL). Other hormonal workup was unremarkable. Ophthalmologic evaluation was consistent with left optic nerve pallor and neural rim thinning suggestive of a guarded prognosis. Immediate neurosurgical intervention was deemed unnecessary. Cabergoline 0.25 mg twice a week was initiated. Subsequently, the PRL levels improved but remained elevated to 414.2 ng/mL and cabergoline dose was increased to 0.5 mg twice a week. MRI Brain after 10 months revealed significant tumor reduction to 2.1 cm x 2.1cm x 1.2 cm. He was inconsistent with his endocrinology follow up appointments and was also non-adherent to cabergoline intermittently. After 14 months of starting DA therapy, he presented with worsening blurriness in his left eye. A repeat brain MRI showed stable appearance of the large pituitary macroadenoma with inferior bowing of the optic chiasm. Significant distortion, tented appearance, and attenuation of the left prechiasmatic optic nerve was also noted. He was evaluated by neuro ophthalmology and a diagnosis of secondary visual deterioration due to optic chiasmal herniation was made. Cabergoline therapy was promptly discontinued. Two weeks post-cabergoline cessation, he underwent trans-sphenoidal resection reporting vision improvement pre-surgery. Post-operative MRI depicted changes with no residual tumor and improved optic chiasm position. Discussion:Various theories explain chiasmal herniation with dopamine agonist (DA) treatment for prolactinomas. Pre-existing chiasm-tumor tethering may exacerbate downward pull during tumor reduction caused by DA therapy. Some case series have suggested that not all patients with chiasmal herniation have visual field defects and that despite improvement in visual fields with decrease in DA dosage, there are no appreciable radiographic changes/reversal of chiasmal herniation. One of the explanations for this lack of correlation is that visual impairment is rather a consequence of vascular compression. This case underscores the need for regular perimetry in macroprolactinoma patients on medical treatment. Adjusting dopamine agonist dosage to allow controlled tumor regrowth, monitored closely with frequent visual field and prolactin assessments, is crucial for relieving optic chiasm tension. Presentation: 6/3/2024

9294 Clinical and Radiological Characterization And Outcomes of Lipid-Poor Adrenal Masses- A Multi-Center Retrospective Study

Abstract Disclosure: V. Balderrama-Brondani: None. R. Al-ward: None. K. Kiseljak-Vassiliades: None. L.M. Fishbein: None. D.A. Kirelik: None. O. Hamidi: None. R. Pishdad: None. H.K. Ghayee: None. M. Sukkari: None. S.S. Bedrose: None. A.H. Hamrahian: None. M.A. Habra: None. Background: Lipid-poor adrenal masses (LPAMs) with pre-contrast radiodensity &amp;gt;10 Hounsfield Units (HU) on computed tomography (CT) represent ∼25% of adrenal tumors. There is limited data about the natural history of LPAMs; therefore, we evaluated a large series of patients with LPAMs to describe the radiological and clinical features and outcomes of these cases. Methods: We conducted a multi-center retrospective cohort study of patients with LPAMs with a baseline diameter of 10-39 mm and derived from 6 institution members of the American-Australian-Asian Adrenal Alliance (A5). We excluded suspected or proven adrenal metastasis, pheochromocytoma, sarcoma, lymphoma, myelolipoma, infiltrative lesions, and adrenal hemorrhage, as well as patients with personal/familial history of genetic predisposition to adrenal neoplasms. The data is presented in percentage and median (range). Results: A total of 242 adrenal masses from 218 patients were evaluated, but only 225 (93%) masses met the inclusion criteria and were analyzed. The age was 58 (23-92), and 61% were women. LPAMs were incidentally discovered in 155 (71.1%) cases, 32 (14.7%) cases were diagnosed due to hormonal overproduction, and 17 (7.8%) due to pain/mass effect. Forty-six (21.1%) patients were on surveillance for a history of extra adrenal malignancy. Masses were unilateral in 89.9% (left side, 57.1%), with size 21 (10-38) mm, with a pre-contrast density of 24 (11-136) HU. Absolute washout was reported in 107 LPAMs and was &amp;gt;60% in 73 (68.2%) cases. The follow-up time was 44.4 (0.9-241) months. Hormonal overproduction developed during the follow-up in 23 (10.5%) cases as follows: cortisol in 15 (6.9%), aldosterone in 4 (1.8%), and sex hormones in 3 (1.4%) cases. LPAM growth rate was 0.03 (-2.18-11.59) cm/year. Seventy-one masses (31.5%) underwent diagnostic procedures (surgery/biopsy) with adrenocortical adenoma (n=37; 52.1%) and adrenocortical carcinoma (ACC) (n=25; 35.2%) being the two most common diagnoses. The tumor growth rate of pathologically confirmed adenomas was 0.03 (-0.30-10.50) cm/year, and of ACC was 1.31 (0.03-11.59) cm/year. A total of 154 (68.4%) LPAMs remained under surveillance at the end of the study, with a follow-up time of 51.8 (6-241) months and a tumor growth rate of 0.02 (-2.18-1.36) cm/year. Forty-five (20.6%) LPAMs decreased by 2 mm (1-13) during the study period. Cases that proved to be ACC had the most significant tumor growth rate over the study (p&amp;lt;0.001). The median time between the initial discovery of LPAM and the surgical resection of ACC cases was 34 (6-128) months. Conclusion: Our study showed that LPAMs carry significant malignant potential, and close long-term follow-up is warranted when surgical resection is not pursued. Prospective studies are critically needed to validate our findings and to establish high-risk molecular, imaging, and biochemical features associated with malignancy. Presentation: 6/2/2024

Aluminum phthalocyanine tetrasulfonate conjugated to surface-modified Iron oxide nanoparticles as a magnetic targeting platform for photodynamic therapy of Ehrlich tumor-bearing mice

BackgroundPhotodynamic therapy (PDT) is a targeted treatment option for cancers that are non-responding to ordinary anticancer therapies. It involves activating a photosensitizer with a light source of a specific wavelength to destroy targeted cells and their surrounding vasculature. Aluminum phthalocyanine tetra sulfonate (AlPcS4) has gained attention as a second-generation photosensitizer for its strong absorption in the red-light region. AlPcS4 can be conjugated to magnetic iron oxide nanoparticles (IONs) to provide targeted drug delivery to the tumor cells while reducing its undesired effect on healthy tissues in other body parts. MethodsMagnetic glutamine functionalized iron oxide nanocomposites loaded with AlPcS4 (IONs-NH2-AlPcS4) were synthesized via the co-precipitation method. The conjugate (IONs-NH2-AlPcS4) was characterized by TEM, Zeta potential, DLS, FTIR, and UV–VIS absorption spectroscopy. Furthermore, its photodynamic activity was investigated using albino mice with induced Ehrlich solid tumors. ResultsAlPcS4 was successfully conjugated to IONs-NH2 with a high loading efficiency of 54±2%. The synthesized conjugate exhibited a spherical shape, with 7 ± 2 nm particle size. The In vivo experiment revealed that the albino mice with induced Ehrlich solid tumor that were treated by combined PDT and magnetic targeting conjugate exhibited significant tumor regression and notably higher levels of necrotic tissue compared to the animals in other groups. ConclusionPDT mediated by magnetic targeting significantly inhibited tumor growth with minimal adverse effects, indicating its great potential as a promising strategy for solid cancer treatment.

Co-delivery of temozolomide and quercetin with folic acid-conjugated exosomes in glioblastoma treatment.

Aim: The study aims to improve glioblastoma multiforme (GBM) treatment by combining temozolomide (TMZ) and quercetin (Qct), using folic acid (FA)-conjugated exosomes to overcome TMZ resistance and enhance blood-brain barrier (BBB) penetration.Methods: Exosomes were isolated and after characterizing and modifying their surfaces with FA, drug loading of TMZ and Qct into exosomes was done. In vitro assays, including cell viability tests, RT-PCR, Western-blotting and flow-cytometry, were performed using U87MG and U251MG GBM cell lines. In vivo analysis included administering exosome-drug formulations to glioblastoma-bearing Wistar rats, monitored through optical imaging and PET scans, followed by post-mortem immunohistochemistry and histological examination.Results: The results showed successful exosome isolation and FA conjugation, with drug release studies indicating accelerated release of TMZ and Qct in acidic conditions, enhancing cytotoxicity. Immunofluorescence indicated greater exosome uptake in GBM cells due to FA conjugation. Cell viability assays demonstrated increased toxicity of the combination therapy, correlating with elevated apoptosis. In vivo studies revealed significant tumor size reduction, alongside increased apoptosis and reduced angiogenesis, particularly in the TMZ-Qct-Exo-FA group.Conclusion: FA-conjugated exosomes loaded with TMZ and Qct represent a promising strategy to enhance GBM treatment efficacy by improving drug delivery, apoptosis induction and inhibiting the PI3K/Akt/mTOR pathway.

New Small-Molecule SERCA Inhibitors Enhance Treatment Efficacy in Lenvatinib-Resistant Papillary Thyroid Cancer.

Papillary thyroid cancer (PTC) is one of the most treatable forms of cancer, with many cases being fully curable. However, resistance to anticancer drugs often leads to metastasis or recurrence, contributing to the failure of cancer therapy and, ultimately, patient mortality. The mechanisms underlying molecular differences in patients with metastatic or recurrent PTC, particularly those resistant to anticancer drugs through epigenetic reprogramming, remain poorly understood. Consequently, refractory PTC presents a critical challenge, and effective therapeutic strategies are urgently needed. Therefore, this study aimed to identify small-molecule inhibitors to enhance treatment efficacy in lenvatinib-resistant PTC. We observed an increase in sarco/endoplasmic reticulum calcium ATPase (SERCA) levels in patient-derived lenvatinib-resistant PTC cells compared with lenvatinib-sensitive ones, highlighting its potential as a therapeutic target. We subsequently identified two SERCA inhibitors [candidates 40 (isoflurane) and 42 (ethacrynic acid)] through in silico screening. These candidates demonstrated significant tumor shrinkage in a xenograft tumor model and reduced cell viability in patient-derived lenvatinib-resistant PTC cells when used in combination with lenvatinib. Our findings have potential clinical value for the development of new combination therapies to effectively target highly malignant, anticancer drug-resistant cancers.

Preoperative Embolization of Glomus Tumors: Role, Effectiveness, and Complications.

Purpose: Paragangliomas represent a surgical challenge due to their hypervascularization. The preoperative selective embolization of these tumors significantly decreases intraoperative blood loss. However, the literature on preoperative embolization in glomus tumors is limited. The aim of this study is to contribute additional evidence regarding the role of preoperative embolization, as well as to evaluate risks and complications in the treatment of glomus tumors. Methods: A retrospective evaluation of all the embolizations of glomus tumors from 2009 to 2023 was conducted. The primary outcome parameter was the rate of devascularization after embolization and the occurrence of significant perioperative hemorrhages. The secondary outcome was embolization-related complications. Results: Twenty-one embolizations in 20 patients were investigated in the study. In 43% of the cases more than 90% devascularization was achieved by embolization, while in the remaining cases, 80 to 90% devascularization was reached. In one case (5%), significant perioperative bleeding after embolization occurred. In one case (5%), a symptomatic complication occurred periinterventionally due to the brief dislocation of the coaxial and microcatheter into the internal carotid artery (ICA), which led to fresh punctate DWI lesions on the subsequent MRI. No patients developed nerve palsy following embolization. Conclusions: The preoperative embolization of glomus tumors can lead to significant tumor devascularization and a reduction in perioperative bleeding, with a low complication rate.

A case of salvage surgery following chemoradiotherapy and durvalumab for initially unresectable superior sulcus tumor with N3 involvement

BackgroundDurvalumab after chemoradiation (PACIFIC regimen) provides favorable treatment outcomes for unresectable stage III non-small cell lung cancer (NSCLC). The feasibility of salvage surgery after the PACIFIC regimen has been reported in some studies; however, its efficacy remains unclear. We herein present the first case of salvage surgery after the PACIFIC regimen for a superior sulcus tumor with N3 involvement, in which a pathological complete response was achieved.Case presentationA 53-year-old man with a left superior sulcus tumor with N3 (# 1L, #4R) involvement (adenocarcinoma, clinical T3N3M0/IIIC) underwent concurrent chemoradiotherapy (2 cycles of cisplatin plus vinorelbine with 60 Gy radiotherapy) followed by durvalumab treatment for 1 year at a previous hospital. The PACIFIC regimen provided a significant primary tumor shrinkage (diameter 3.1 cm to 0.5 cm) with the disappearance of 18F-fluorodeoxyglucose uptake in all nodes. Six months after the end of the PACIFIC regimen, only the primary tumor showed enlargement (diameter 0.5 cm to 2.0 cm). Accordingly, local tumor recurrence was suspected. Salvage surgery (left upper lobectomy with combined chest wall resection [1st to 4th rib]) was performed. The histological examination revealed no viable tumor cells (ypT0N0M0). At 7 months after salvage surgery, the patient remains alive with no signs of tumor recurrence.ConclusionsThe present case suggests that salvage surgery may be feasible after the PACIFIC regimen for superior sulcus tumors. A long-term follow-up is essential to determine the efficacy of salvage surgery.

The Efficacy and Safety of Bevacizumab Plus Anti-PD-1/PD-L1 Inhibitors in Combination with Hepatic Arterial Infusion Chemotherapy for Initially Unresectable Hepatocellular Carcinoma.

To report the efficacy and safety of triple combination therapy with bevacizumab plus anti-PD-1 (BP1) or anti-PD-L1 inhibitors (BPL) combined with hepatic arterial infusion chemotherapy (HAIC) as a first-line treatment for initially unresectable hepatocellular carcinoma (uHCC). In this retrospective study, patients with initially uHCC received either BP1-HAIC or BPL-HAIC as first-line treatment. The primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS), objective response rate (ORR) and disease control rate (DCR). Between January 2020 and December 2022, a total of 136 patients with initially uHCC received triple combination therapy, with 76 in the BP1-HAIC group and 60 in the BPL-HAIC group. The median PFS for the entire cohort was 11.1 months (95% CI, 8.0-13.7 months), and the median OS was 22.4 months (95% CI, 21.3- not reached). Comparative analysis revealed no significant differences in PFS (HR, 0.91, P = 0.69) or OS (HR, 0.71, P = 0.31) between the BP1-HAIC and BPL-HAIC groups. The ORR was 46.3% per RECIST v1.1 and 66.9% per mRECIST, with a DCR of 83.1% under both criteria. Common adverse events (AEs) included hypoalbuminemia and elevated aspartate/alanine aminotransferase, with 5.1% (7/136) experienced upper gastrointestinal bleeding. Multivariate Cox analysis identified tumor number and BCLC stage as independent prognostic factors for OS, and tumor number for PFS. Triple combination therapy demonstrated significant therapeutic efficacy and tumor response in initially uHCC. No notable differences in outcomes were observed between the BP1-HAIC and BPL-HAIC groups. AEs were manageable in clinical practice.

Temozolomide Therapy in Management of Refractory Pituitary Adenomas: A Case Series of 39 Patients

ObjectiveThe management of refractory pituitary adenomas (RPAs) presents significant challenges. This study aimed to evaluate the long-term treatment outcomes of patients with RPA managed with temozolomide (TMZ) and to identify potential biomarkers for predicting TMZ treatment response. MethodsThis retrospective case series included patients with RPA who underwent trans-sphenoidal surgery (TSS) or craniotomy at a comprehensive medical center in China between January 2014 and December 2021. Results39 patients with RPA (median age 42 years; 23 males [59%]) were treated with TMZ for a median of 9 cycles. The median follow-up was 34.4 months. Complete response (CR) was observed in 2 patients, partial response (PR) in 11 patients, stable disease (SD) in 9, progressive disease (PD) in 11, and death in 6 patients. O6-methylguanine DNA methyltransferase levels were significantly lower in patients with CR, PR, or SD compared to those with PD or mortality, with mean values of 24.2% and 58.1, respectively. MutS homologs 6 levels were significantly higher in patients with CR, PR, or SD compared to those with PD or mortality, with mean values of 64.2% and 36.9%, respectively. Patients who received concomitant TMZ and external beam radiotherapy showed a significant tumor size reduction of 178,837 mm3 (P < .001) compared to those treated with TMZ alone. ConclusionsTMZ demonstrates promising efficacy in eliciting tumor responses in patients with PRA. O6-methylguanine DNA methyltransferase and MutS homologs 6 have emerged as potential biomarkers for predicting treatment response. Furthermore, radiation with concurrent TMZ may significantly improve outcomes in patients with RPA.