Predominant Tumor Research Articles

Clinicopathological assessment of renal tumors in pediatric age group in a sample of Iraqi patients

Background: According to the Iraqi Cancer Registry, renal carcinoma is the 13th most common carcinoma, with 798 registered cases in 2020 and 418 deaths. Methods: This is a cross sectional retrospective study that includes the analysis of 116 randomly selected sample of pediatric patients (74 nephrectomies and 42 biopsies) sent to the Teaching Laboratories of AL-Emamain AL-Kadhmain city (AS), Baghdad medical city, and private laboratories from January 2019 to January 2023. Results: Histopathological diagnosis revealed a ratio from malignant to benign of 7.4:1. Wilm’s tumor was the most common malignant tumor (65.5%), while multicystic renal dysplasia was the most common benign tumor (7.8%). Abdominal pain was the most common clinical feature (67.2%), followed by abdominal mass (20.7%). Regarding malignant cases, Pathological stage I was the most common (39.0%). As for the histopathological subtype, triphasic type was the most common (57.1%), followed by the biphasic type (10.5%). Conclusions, Malignant tumors make up the vast majority of renal tumors. Wilm tumor is the predominant malignant tumor. Fortunately, most cases of Wilm tumors exhibited an early stage and favorable histology. Neuroblastoma was the second most common malignant tumor. The abdominal lump is the most common presentation of pediatric renal tumor.

Nano-Based Drug Delivery Systems: Potential Developments in the Therapy of Metastatic Osteosarcoma-A Narrative Review.

Osteosarcoma, a predominant malignant bone tumor, poses significant challenges due to its high metastatic and recurrent nature. Although various therapeutic strategies are currently in use, they often inadequately target osteosarcoma metastasis. This review focuses on the potential of nanoscale drug delivery systems to bridge this clinical gap. It begins with an overview of the molecular mechanisms underlying metastatic osteosarcoma, highlighting the limitations of existing treatments. The review then transitions to an in-depth examination of nanoscale drug delivery technologies, emphasizing their potential to enhance drug bioavailability and reduce systemic toxicity. Central to this review is a discussion of recent advancements in utilizing nanotechnology for the potential intervention of metastatic osteosarcoma, with a critical analysis of several preclinical studies. This review aims to provide insights into the potential applications of nanotechnology in metastatic osteosarcoma therapy, setting the stage for future clinical breakthroughs and innovative cancer treatments.

A RARE PRESENTATION OF SMALL CELL LUNG CARCINOMA METASTASIZING TO PHEOCHROMOCYTOMA

Abstract Introduction/Objective Tumor-to-tumor metastasis is a rare phenomenon in which primary tumor cells metastasize hematogenously into another unrelated tumor. We report an interesting case of a tumor-to-tumor metastasis of small cell lung carcinoma to pheochromocytoma of the adrenal gland. Methods/Case Report A 75-year-old female former cigarette smoker with a past medical history of hypertension presented with a two-day history of dyspnea and epigastric pain. Physical examination demonstrated elevated blood pressure only. A computerized axial tomography scan of the chest and abdomen showed an incidental 3.1 cm right adrenal mass and right hilar lymphadenopathy. Detailed biochemical workup showed elevated serum epinephrine, norepinephrine, and 24-hour urine metanephrine. Adrenalectomy showed a 5.8 cm tumor mass with solid lobulated yellow to pink-tan and focally hemorrhagic cut surfaces. Microscopic examination showed a neoplasm composed of two distinct components. The predominant component consisted of nests ("zellballen") of large polygonal cells with variable nuclear pleomorphism, abundant amphophilic to basophilic cytoplasm, and a delicate intervening fibrovascular stroma, without significant mitotic activity. The minor component was characterized by sheets and nests of "small blue cells" with round to ovoid nuclei, stippled nuclear chromatin pattern, scanty cytoplasm, patchy necrosis, and high mitotic activity (>20 mitoses per 10 HPF). Foci of small cell carcinoma deposits were also present in the lymphatic channels of pheochromocytoma. Immunohistochemical stains demonstrated cytoplasmic staining of predominant component tumor cells for synaptophysin, chromogranin, and the absence of staining for TTF-1, CK CAM 5.2, and Ki-67. However, minor component tumor cells demonstrated cytoplasmic staining for synaptophysin, membranous staining for CK CAM 5.2, and nuclear staining for TTF-1 and Ki-67(60%). A final diagnosis of composite pheochromocytoma (predominant) and small cell neuroendocrine carcinoma (minor) was rendered. The possibility of a” collision” tumor comprising primary small cell carcinoma of pulmonary origin metastatic to an adrenal pheochromocytoma in light of the patient's cigarette smoking history and the presence of right hilar lymphadenopathy was favored. The subsequent biopsy of the right subcarinal adenopathy showed small cell carcinoma. Results (if a Case Study enter NA) NA Conclusion To the best of our knowledge, this is the only case of metastasis to a pheochromocytoma from a small cell neuroendocrine lung carcinoma.

Pediatric craniopharyngiomas: magnetic resonance imaging assessment for hypothalamus-pituitary axis dysfunction and outcome prediction.

In adamantinomatous craniopharyngiomas, tumor topographical categories, cystic component volume, and magnetic resonance signal intensity may impact prognosis. To identify magnetic resonance imaging (MRI) variables associated with pituitary-hypothalamic axis dysfunction and predictive of outcome in children with cystic adamantinomatous craniopharyngiomas. We evaluated 40 preoperative MRIs of adamantinomatous craniopharyngiomas to classify tumor topography, volume, and signal intensity of the cystic components and peritumoral edema. Volumes and normalized signal intensity minimum values were extracted from coronal T2-weighted images (nT2min). Radiological variables were compared to pituitary-hypothalamic axis dysfunction-related clinical data and surgical outcomes. Adamantinomatous craniopharyngiomas were categorized into five topographic classes (12 patients, sellar-suprasellar; seven patients, pseudo-intraventricular; six patients, strict intraventricular; 14 patients, secondary intraventricular; one patient, not strict intraventricular). All cases exhibited a predominant (30 patients, 80%) or total (10 patients, 20%) cystic tumor component and displayed low nT2min percentage values compared to cerebrospinal fluid (42.3% [interquartile range 28.4-54.6%]). Significant associations between tumor topographic classes and pituitary dysfunction (P<0.001), andbetween peritumoral edema and hypothalamic dysfunction (P<0.001) were found. Considering extent of surgical removal and tumor relapse, volume of the cystic tumor component displayed a positive correlation (P=0.002; r=0.48; P=0.02; r=0.36), while nT2min intensity values exhibited a negative correlation (P=0.01; r= - 0.40; P=0.028; r= - 0.34). Severe hypothalamic-pituitary axis dysfunction is associated with tumors along the pituitary stalk and peritumoral edema. Tumor invasion of the third ventricle, tight adherence to the hypothalamus, larger volumes, and lower nT2min intensity of the tumor cystic component are independent predictors of extent ofadamantinomatous craniopharyngioma excision and recurrence.

Neurological adverse events related to immune-checkpoint inhibitors in Spain: a retrospective cohort study

Neurological immune-related adverse events associated with immune checkpoint inhibitors can have several clinical manifestations, but the syndromes and prognostic factors are still not well known. We aimed to characterise and group the clinical features, with a special focus in patients presenting with encephalopathy, and to identify predictors of response to therapy and survival. This retrospective observational study included patients with neurological immune-related adverse events from 20 hospitals in Spain whose clinical information, serum samples, and CSF samples were studied at Hospital Clinic de Barcelona, Barcelona, Spain. Patients with pre-existing paraneoplastic syndromes or evidence of alternative causes for their neurological symptoms were excluded. We reviewed the clinical information, classified their clinical features, and determined the presence of neural antibodies. Neurological status was assessed by the treating physician one month after adverse event onset (as improvement vs no improvement) and at the last evaluation (complete recovery or modified Rankin Scale score decrease of at least 2 points, indicating good outcome, vs all other modified Rankin Scale scores, indicating poor outcome); if the participant had died, the date and cause of death were recorded. We used Fisher's exact tests and Mann-Whitney U tests to analyse clinical features, and multivariable logistic regression to analyse prognostic factors. From Jan 1, 2018, until Feb 1, 2023, 83 patients with suspected neurological immune-related adverse events after use of immune checkpoint inhibitors were identified, of whom 64 patients were included. These patients had a median age of 67 years (IQR 59-74); 42 (66%) were male and 22 (34%) were female. The predominant tumours were lung cancer (30 [47%] patients), melanoma (13 [21%] patients), and renal cell carcinoma (seven [11%] patients). Neural antibodies were detected in 14 (22%) patients; 52 (81%) patients had CNS involvement and 12 (19%) had peripheral nervous system involvement. Encephalopathy occurred in 45 (70%) patients, 12 (27%) of whom had antibodies or well defined syndromes consistent with definite paraneoplastic or autoimmune encephalitis, 24 (53%) of whom had encephalitis without antibodies or clinical features characteristic of a defined syndrome, and nine (20%) of whom had encephalopathy without antibodies or inflammatory changes in CSF or brain MRI. Nine (14%) of 64 patients had combined myasthenia and myositis, five of them with myocarditis. Even though 58 (91%) of 64 patients received steroids and 31 (48%) of 64 received additional therapies, 18 (28%) did not improve during the first month after adverse event onset, and 11 of these 18 people died. At the last follow-up for the 53 remaining patients (median 6 months, IQR 3-13), 20 (38%) had a poor outcome (16 deaths, one related to a neurological immune-related adverse event). Mortality risk was increased in patients with lung cancer (vs those with other cancers: HR 2·5, 95% CI 1·1-6·0) and in patients with encephalopathy without evidence of CNS inflammation or combined myocarditis, myasthenia, and myositis (vs those with the remaining syndromes: HR 5·0, 1·4-17·8 and HR 6·6, 1·4-31·0, respectively). Most neurological immune-related adverse events involved the CNS and were antibody negative. The presence of myocarditis, myasthenia, and myositis, of encephalopathy without inflammatory changes, or of lung cancer were independent predictors of death. Most deaths occurred during the first month of symptom onset. If our findings are replicated in additional cohorts, they could confirm that these patients need early and intensive treatment. The Instituto de Salud Carlos III and the European Union.

CSIG-20. SYSTEMATIC REVIEW OF MOLECULAR TARGETED THERAPIES FOR ADULT-TYPE DIFFUSE GLIOMA: AN ANALYSIS OF CLINICAL AND LABORATORY STUDIES

Abstract Gliomas are becoming a frequent topic of investigation for molecular-targeted therapies. However, the current state of research in this area, particularly following the 2021 WHO guideline change, remains undefined. This systematic review sought to characterize the current state of molecular target therapy research for adult-type diffuse glioma to inform scientific progress. A systematic review was conducted in accordance with PRISMA guidelines. Studies meeting inclusion criteria were queried for study design, tumor type, molecular target, molecular pathway, and details pertaining to the molecular targeted therapy– namely the modality, dose, duration of treatment. 350 studies met inclusion criteria: 52 of these were clinical studies, 190 were laboratory studies investigating existing molecular therapies, and 108 were laboratory studies investigating new molecular targets. 119 ongoing clinical trials are also underway, per a detailed query of clinicaltrials.gov. GBM was the predominant tumor studied, with few studies mentioning IDH-mutant astrocytoma or oligodendroglioma. The most common molecular targets in published clinical studies and clinical trials were protein kinase pathways, followed by microenvironmental targets, then immunotherapy and cell cycle/apoptosis pathways. The most common molecular targets in laboratory studies were protein kinase pathways, followed by cell cycle/apoptosis, microenvironmental targets, then immunotherapy pathways, with the wnt/β-catenin pathway arising as a novel target. This systematic review examined the current evidence on molecular targeted therapy for adult-type diffuse glioma and discusses its implications for clinical practice and future research. Published research encompasses clinical studies, laboratory testing of existing therapies, and identification of novel targets, with GBM as the focal point. Ongoing clinical trials are numerous in this area of research as well and follow a similar pattern in tumor type and targeted pathways as published clinical studies. The most common molecular targets were protein kinase pathways, with some variation in the prevalence of other pathways depending on study type.

Estimating the cure proportion of stage IA lung adenocarcinoma: a population-based study

BackgroundWe aimed to investigate the factors influencing the cure, recurrence, and metastasis rates of stage IA lung adenocarcinoma, using a mixed cure model.MethodsA total of 1,064 patients who underwent video-assisted thoracoscopic pulmonectomy were included. Variable screening was performed using the random forest algorithm and least absolute shrinkage and selection operator approaches. The mixed cure model was used to identify factors affecting patient cure and survival, and a sequential analysis was performed on 5%, 10%, and 20% of the presentational subtype concurrently. A receiver operating characteristics curve was used to determine the best model and construct a nomogram to predict the cure rate.ResultsThe median follow-up time was 58 (range: 3–115) months. Results from the cure part of the mixed model indicated that the predominant subtype, presentational subtype, and tumor diameter were the main prognostic factors affecting cure rate. Therefore, the nomogram to predict the cure rate was constructed based on these factors. The survival part indicated that the predominant subtype was the only factor that influenced recurrence and metastasis. A sequential analysis of the presentational subtype showed it had no significant effect on survival (P > 0.05). Regardless of the recording mode, no significant improvement was observed in the model's discriminative ability. Only a few postoperative pathological specimens showed lymphovascular invasion (LVI); however, the survival curve suggested a significant effect on patient survival.ConclusionsAfter excluding the existence of long-term survivors, the predominant tumor subtype was determined to be the only factor influencing recurrence and metastasis. Although LVI is rare in stage IA lung adenocarcinoma, its significance cannot be discounted in terms of determining patient prognosis.

A retrospective study of cerebellopontine angle tumours: A single instituitional study

: Cerebellopontine angle (CPA) tumors are rare intracranial neoplasms that arise in the region between the cerebellum and the pons. These tumors can be challenging to treat due to their complex anatomy and proximity to critical neurovascular structures. Surgical intervention is often necessary to achieve a favorable outcome. The primary objectives of this retrospective study are to analyze the clinical and radiological characteristics of cerebellopontine angle tumors, identify pathological types, assess surgical resectability, and evaluate postoperative outcomes.: The study enrolled 14 patients who underwent surgical intervention for cerebellopontine angle tumors at Armed forces medical college, Pune. A retrospective analysis was performed, considering demographic data, clinical presentations, imaging characteristics and surgical outcomes.: Vestibular schwannoma was the predominant tumor type with majority of tumors manifesting between third to fifth decades. Clinical manifestation included SNHL, cerebellar dysfunction, headache and sensory trigeminal dysfunction. A substantial proportion (86%) presented with no useful hearing preoperatively. Surgical outcomes indicated varying degrees of success, with total resection achieved in a subset of cases. Notably, anatomical preservation of the facial nerve was accomplished in a significant proportion of patients. Postoperative assessments, using the House Brackmann system, revealed positive facial nerve function outcomes in a substantial percentage. Complications included cerebrospinal fluid leak (14%), meningitis(7%) and lower cranial nerve paresis (7%). : In conclusion, surgical intervention plays a crucial role in the management of cerebellopontine tumors. The choice of surgical approach should be individualized based on tumor characteristics and patient factors, with the goal of achieving maximum tumor resection while minimizing complications. Further research and advancements in surgical techniques are needed to optimize outcomes for patients with cerebellopontine tumors.

Time-to-event overall survival prediction in glioblastoma multiforme patients using magnetic resonance imaging radiomics

PurposeGlioblastoma Multiforme (GBM) represents the predominant aggressive primary tumor of the brain with short overall survival (OS) time. We aim to assess the potential of radiomic features in predicting the time-to-event OS of patients with GBM using machine learning (ML) algorithms.Materials and methodsOne hundred nineteen patients with GBM, who had T1-weighted contrast-enhanced and T2-FLAIR MRI sequences, along with clinical data and survival time, were enrolled. Image preprocessing methods included 64 bin discretization, Laplacian of Gaussian (LOG) filters with three Sigma values and eight variations of Wavelet Transform. Images were then segmented, followed by the extraction of 1212 radiomic features. Seven feature selection (FS) methods and six time-to-event ML algorithms were utilized. The combination of preprocessing, FS, and ML algorithms (12 × 7 × 6 = 504 models) was evaluated by multivariate analysis.ResultsOur multivariate analysis showed that the best prognostic FS/ML combinations are the Mutual Information (MI)/Cox Boost, MI/Generalized Linear Model Boosting (GLMB) and MI/Generalized Linear Model Network (GLMN), all of which were done via the LOG (Sigma = 1 mm) preprocessing method (C-index = 0.77). The LOG filter with Sigma = 1 mm preprocessing method, MI, GLMB and GLMN achieved significantly higher C-indices than other preprocessing, FS, and ML methods (all p values < 0.05, mean C-indices of 0.65, 0.70, and 0.64, respectively).ConclusionML algorithms are capable of predicting the time-to-event OS of patients using MRI-based radiomic and clinical features. MRI-based radiomics analysis in combination with clinical variables might appear promising in assisting clinicians in the survival prediction of patients with GBM. Further research is needed to establish the applicability of radiomics in the management of GBM in the clinic.

GPX8 regulates pan-apoptosis in gliomas to promote microglial migration and mediate immunotherapy responses.

Gliomas have emerged as the predominant brain tumor type in recent decades, yet the exploration of non-apoptotic cell death regulated by the pan-optosome complex, known as pan-apoptosis, remains largely unexplored in this context. This study aims to illuminate the molecular properties of pan-apoptosis-related genes in glioma patients, classifying them and developing a signature using machine learning techniques. The prognostic significance, mutation features, immunological characteristics, and pharmaceutical prediction performance of this signature were comprehensively investigated. Furthermore, GPX8, a gene of interest, was extensively examined for its prognostic value, immunological characteristics, medication prediction performance, and immunotherapy prediction potential. Experimental techniques such as CCK-8, Transwell, and EdU investigations revealed that GPX8 acts as a tumor accelerator in gliomas. At the single-cell RNA sequencing level, GPX8 appeared to facilitate cell contact between tumor cells and macrophages, potentially enhancing microglial migration. The incorporation of pan-apoptosis-related features shows promising potential for clinical applications in predicting tumor progression and advancing immunotherapeutic strategies. However, further in vitro and in vivo investigations are necessary to validate the tumorigenic and immunogenic processes associated with GPX8 in gliomas.

Clinicopathological profile of breast cancer from Chhattisgarh India: A single-center hospital-based study.

Global breast cancer incidence is increasing at an annual rate of 3·1%. Female breast cancer has surpassed lung cancer as the most commonly diagnosed cancer, with an estimated 2.3 million new cases (11.7%). However, the data from different parts of India are still lacking and the study was conducted to assess the burden of disease at tertiary referral centers in central India. Retrospective record analysis (June 2013-June 2017) of data from outdoor clinics and pathology reports. The patients aged <15 yrs, nonresidence of Chhattisgarh, and diagnosed outside the study period were excluded. The triple assessment was used to diagnose all breast lumps (sensitivity 99%). Eighty patients were diagnosed having breast carcinoma. The mean age for breast cancer was 39 ± 3.028 years (ranged 31-50 years). Twenty patients had locally advanced breast carcinoma. The predominant religion was Hindu 55.00%. The referral pathway to seek medical care for breast cancer was via a gynecologist in 40% (32/80). Familial breast cancers were in 0.03% (3/80) of patients. None breast cancer patients have previous histology-proven benign breast disease. The mean size of the breast cancer lump was 3.56 cm (ranged 1.0-11.0 cm). Overlying skin ulceration (n = 2), skin infiltration/peau-d'- orange (n = 2), skin tethering (n = 4), and bloody nipple discharge were found in one patient. Breast cancer was diagnosed during lactation (postnatal period) in one patient. The maximum number of patients have tumor size >5 cm (72.6%). Immunohistochemistry and pathological analysis was done on core biopsy (n = 20) and surgical procedure (n = 60). Modified radical mastectomy was done in 52, breast conservative surgery with Sentinal Lymph node biopsy and axillary lymph node dissection in 6, and toilet mastectomy in two patients. The predominant tumors were solid (n = 79/80), with both solid and cystic types (1/80). The solid and cystic lesion on FNAC was of C3b type, and an excision biopsy revealed medullary carcinoma of the breast. Invasive ductal carcinoma-no special type (IDC-NST) was observed to be the most common histopathologic type (n = 70/80), followed by medullary carcinoma (n = 2), metaplastic carcinoma (n = 1), papillary carcinoma (n = 4), Paget disease with DCIS (n = 1), mucinous carcinoma (n = 1), invasive lobular carcinoma (n = 1). One male patient with breast cancer and two female patient having bilateral breast cancer also have IDC-NST.Scarff Bloom Richardson Grade was predominantly graded 2 in 46.25% (37/80) of breast cancer patients (Grade 1 = 9, Grade 2 = 37, Grade 3 = 34). Lymphovascular (LVI) and perineural invasion (PNI) were predominantly without LVI and PVI. (Lymphovascular present and perineural invasion present = 4, Lymphovascular present and perineural invasion absent = 32, Lymphovascular absent and perineural invasion absent = 42, Lymphovascular absent and perineural invasion present = 2). Histological examination of axillary lymph nodes showed the presence of malignant cells in all. Triple-negative breast carcinoma was 26.58% (21/79). Most breast cancer presented at stage II A = 37.5% (30/80) and II B = 28.7% (23/80) of the AJCC staging system. The clinico-epidemio and histological profile of breast cancer in Chhattisgarh is similar to other parts of India. Scarff Bloom Richardson Grade was predominantly grade 2 in 46.25% (37/80) contrary to Grade III (70%) in other series from India.

Assessing the Antiproliferative Potential of a Novel Combretastatin A4 Derivative via Modulating Apoptosis, MAPK/ERK and PI3K/AKT Pathways in Human Breast Cancer Cells.

Breast cancer is the most predominant tumor in women. Even though current medications for distinct breast cancer subtypes are available, the non-specificity of chemotherapeutics and chemoresistance imposes major obstacles in breast cancer treatment. Although combretastatin A-4 (CA-4) has been well-reported to have potential anticancer activity, in vivo studies of CA-4 reveal a decrease in its activity. In this respect, a series of CA-4 analogues have been designed, from which one analog [(1-(3-chloro-4-fluorophenyl)-N-(2methoxyphenyl)-5-(3,4,5-trimethoxyphenyl)-1H-1,2,4-triazole-3-carboxamide, C25H22ClFN4O5] showed drastic cytotoxicity against breast cancer cells. Therefore, this research focused on investigating the in vitro molecular mechanism underlying the cytotoxicity of the CA-4 analogue, particularly the MAPK/ERK as well as PI3K/AKT pathways as attractive therapeutic targets in breast cancer. The cell viability of MCF-7, MDA-MB231, and MDA-MB453 was assessed after treatment with the CA-4 analogue, and apoptosis was analyzed via Annexin V-FITC/PI dual staining. MAPK/ERK and PI3K/AKT were thoroughly assessed using western blotting. Real-time PCR was used to estimate apoptosis-related markers, including the P53, Bcl-2-associated X protein (Bax), and B-cell lymphoma 2 (Bcl2) genes. The CA-4 analogue reduced the survival of all cancerous cells in a concentration-dependent manner and induced apoptosis through the mitochondrial pathway (39.89 ± 1.5%, 32.82 ± 0.6%, and 23.77 ± 1.1% in MCF-7, MDA-MB231, and MDA-MB453 cells), respectively. The analogue also attenuated the expression of pMEK1/2/t-MEK1/2, p-ERK1/2/t-ERK1/2, p-PI3K/t-PI3K, and p-AKT/t-AKT proteins in all three cancer cell lines in a time-dependent manner. Furthermore, the CA-4 analogue upregulated the expression of the P53 gene and dramatically increased the ratio of Bax/Bcl2 genes. The enhanced cytotoxicity can be attributed to substituting the hydroxyl group in CA-4 with chlorine in the meta-position of ring B, substituting the para-methoxy group in CA-4 with fluorine in the analogue, and lastly, introducing an extension to the compound's structure (ring C). Therefore, CA-4 analogue can attenuate the proliferation of human breast cancer cells by inducing apoptosis and simultaneously suppressing the MAPK/ERK and PI3K/AKT pathways.

Sense and nonsense of yT-staging on MRI after chemoradiotherapy in rectal cancer.

The aim of this work was to investigate the value of rectal cancer T-staging on MRI after chemoradiotherapy (ymrT-staging) in relation to the degree of fibrotic transformation of the tumour bed as assessed using the pathological tumour regression grade (pTRG) of Mandard as a standard of reference. Twenty two radiologists, including five rectal MRI experts and 17 'nonexperts' (general/abdominal radiologists), evaluated the ymrT stage on the restaging MRIs of 90 rectal cancer patients after chemoradiotherapy. The ymrT stage was compared with the final ypT stage at histopathology; the percentages of correct staging (ymrT = ypT), understaging (ymrT < ypT) and overstaging (ymrT > ypT) were calculated and compared between patients with predominant tumour at histopathology (pTRG4-5) and patients with predominant fibrosis (pTRG1-3). Interobserver agreement (IOA) was computed using Krippendorff's alpha. Average ymrT/ypT stage concordance was 48% for the experts and 43% for the nonexperts; ymrT/ypT stage concordance was significantly higher in the pTRG4-5 subgroup (58% vs. 41% for the pTRG1-3 group; p = 0.01), with the best results for the MRI experts. Overstaging was the main source of error, especially in the pTRG1-3 subgroup (average overstaging rate 38%-44% vs. 13%-55% in the pTRG4-5 subgroup). IOA was higher for the expert versus nonexpert readers (α = 0.67 vs. α = 0.39). ymrT-staging is moderately accurate; accuracy is higher in poorly responding patients with predominant tumour but low in good responders with predominant fibrosis, resulting in significant overstaging. Radiologists should shift their focus from ymrT-staging to detecting gross residual (and progressive) disease, and identifying potential candidates for organ preservation who would benefit from further clinical and endoscopic evaluation to guide final treatment planning.

Skip metastasis at the esophageal resection margin in radical gastrectomy: clinical characteristics of 30 cases

Objective: To summarize the clinical characteristics of patients with skip metastasis at esophageal resection margin during radical gastrectomy. Methods: This is a descriptive study of case series. Relevant data from 2006 to 2022 were collected from two major gastric cancer consultation and treatment centers: Nanjing Drum Tower Hospital and Jinling Hospital.Characteristics, surgical approach, number of dissected lymph nodes, immunohistochemical staining, and pathological staging were summarized and analyzed. The distribution of residual tumor cells at the esophageal margins was further analyzed at the cellular and tissue levels. Skip metastasis at the esophageal resection margin was defined as a negative esophageal margin with a positive margin in the cephalad donut. Results: Thirty (0.33%, 30/8972) eligible patients, 24 (80.0%) of whom were male, were identified in the two centers. The mean age was 63.9±11.0 years. Seventeen (56.7%) of these patients had papillary or tubular adenocarcinomas, including 13 (43.3%) poorly- and four (13.3%) moderately-differentiated tumors; four (13.3%) had signet-ring cell carcinomas; four (13.3%) mucinous adenocarcinomas; three (10.0%) mixed adenocarcinomas, including two with poorly-differentiated tubular adenocarcinomas mixed with signet-ring cell carcinoma and mucinous adenocarcinoma; and one had a poorly differentiated tubular adenocarcinoma mixed with signet-ring cell carcinoma. Two patients (6.7%) had other types of cancer, namely adenosquamous carcinoma in one patient and undifferentiated carcinoma in the other one. The predominant tumor sites were the lesser curvature (n=26, 86.7%) and the cardia (n=24, 80.0%). The mean tumor diameter was 6.6 cm, mean distance between tumor and esophageal resection margin was 1.5 cm, and proportions of tumor invasion into the dentate line, nerves, and vessels were 80.0% (24/30), 86.7%(26/30), and 93.3% (28/30), respectively. The mean number of lymph nodes resected was 20.4±8.9. The pathological stage was mainly T4 (n=18, 60.0%) and N3 (n=21, 70.0%), the median Ki67 was 52.7%, and the rates of positivity for HER2, EGFR, VEGFR, E-cadherin and PD-L1 were 40.0% (12/30), 46.7% (14/30), 80.0% (24/30), 86.7% (26/30) and 16.7% (5/30), respectively. At the cellular level, cancer cells were mainly distributed in small focal areas, as cell masses, or as tumor thrombi; large numbers of widely distributed atypic cells were seldom observed. At the tissue level, cancer cells were located in the mucosal layer in seven patients (23.3%), in the submucosal layer in 18 (60.0%), and in the muscular layer in five (16.7%); no cancer cells were identified in the outer membrane. Five of the seven tumors were located in the lamina propria, two in the muscularis mucosae, and none in the mucosal epithelium. Conclusion: Patients with skip metastasis at the esophageal resection margin at radical gastrectomy have unfavorable tumor biology and a high proliferation index, are at a late pathological stage, and the residual cancer is mostly located in the submucosa.

Contralateral supraorbital eyebrow approach for tuberculum sellae meningioma.

The main challenge in tuberculum sellae meningioma (TSM) resection is the safe dissection of the optic nerves, which many a times are compressed and distorted by the tumor. While intuitive, an approach from the side of predominant tumor extension makes tumor dissection from the medial surface of the ipsilateral optic nerve rather blind. We describe here a contralateral supraorbital eyebrow approach (c-SEA) to address this "blind spot." c-SEA was performed using a 2 × 2 cm craniotomy. The patient improved after surgery and postoperative imaging confirmed the totality of the tumor resection. c-SEA can be an excellent minimally invasive option for asymmetric TSM.

Deciphering the Signaling Mechanisms of Osteosarcoma Tumorigenesis.

Osteosarcoma (OS) is the predominant primary bone tumor in the pediatric and adolescent populations. It has high metastatic potential, with the lungs being the most common site of metastasis. In contrast to many other sarcomas, OS lacks conserved translocations or genetic mutations; instead, it has heterogeneous abnormalities, including somatic DNA copy number alteration, ploidy, chromosomal amplification, and chromosomal loss and gain. Unfortunately, clinical outcomes have not significantly improved in over 30 years. Currently, no effective molecularly targeted therapies are available for this disease. Several genomic studies showed inactivation in the tumor suppressor genes, including p53, RB, and ATRX, and hyperactivation of the tumor promoter genes, including MYC and MDM2, in OS. Alterations in the major signaling pathways, including the PI3K/AKT/mTOR, JAK/STAT, Wnt/β-catenin, NOTCH, Hedgehog/Gli, TGF-β, RTKs, RANK/RANKL, and NF-κB signaling pathways, have been identified in OS development and metastasis. Although OS treatment is currently based on surgical excision and systematic multiagent therapies, several potential targeted therapies are in development. This review focuses on the major signaling pathways of OS, and we propose a biological rationale to consider novel and targeted therapies in the future.

LES SARCOMES DES TISSUS MOUS : ETUDE PROSPECTIVE SUR 45 PATIENTS

Abstract Aim: The objective of this study is to assess the management of soft tissue sarcomas at the Joliot Curie Institute in Dakar. Patients and Methods: A prospective study was conducted over a span of four years. The parameters examined included epidemiological, diagnostic, therapeutic, and prognostic aspects. Results: A total of 45 patients were included, with an average age of 37.9 years. The predominant tumor site was the lower limb, accounting for 68% of cases (n=32). The average time for the consultation was 31 months. Imaging modalities included CT scans for 25 patients (53.2%) and MRI for 19 patients (40.42%). Dermatofibrosarcoma was the predominant histological type (13 cases/27.5%). Surgery was performed on 41 patients, while 2 patients underwent radiotherapy. During the follow-up period, 9 recurrences and 9 deaths were recorded. Adverse prognostic factors included tumor size exceeding 5 centimeters (37 patients), involved margins (15 patients), and a high histological grade (21 patients). Conclusion:Soft tissue sarcomas are rare and widespread. While surgery remains the primary curative approach, early diagnosis can significantly enhance the quality of care and patient outcomes. Keywords: sarcoma, soft tissue, surgery, radiotherapy, chemotherapy.

Should Redo Surgery be Offered to Patients with Relapsed Glioblastoma? - Outcome Analyses of a Single Institution Comparative Cohort Study

Glioblastoma multiforme (GBM) is the predominant malignant brain tumor originating intracranially. The established first-line treatment postsurgery is concurrent chemoradiation as a definitive measure. However, recurrent GBM's pose a challenge for clinicians who rely on institutional experience to determine the most suitable course of action. Second-line chemotherapy may be administered with or without surgery depending on the institution's practice. This study aims to present our tertiary center institution's experience with recurrent GBM patients who underwent redo surgery. In this retrospective study we analyzed the surgical and oncological data of patients with recurrent GBM who underwent redo surgery at the Royal Stoke University Hospitals between 2006 and 2015. The group 1 (G1) comprised the reviewed patients, while a control group (G2) was randomly selected, matching the reviewed group by age, primary treatment, and progression-free survival (PFS). The study collected data on various parameters, including overall survival, PFS, extent of surgical resection, and postoperative complications. This retrospective study included 30 patients in G1 and 32 patients in G2, matched based on age, primary treatment, and PFS. The study found that the overall survival for the G1 group from the time of first diagnosis was 109 weeks (45-180) compared to 57 weeks (28-127) in the G2 group. The incidence of postoperative complications after the second surgery was 57%, which included hemorrhage, infarction, worsening neurology due to edema, cerebrospinal fluid leak, and wound infection. Furthermore, 50% of the patients in the G1 group who underwent redo surgery received second-line chemotherapy. Our study found that redo surgery for recurrent GBM is a viable treatment option for a select group of patients with good performance status, longer PFS from primary treatment, and compressive symptoms. However, the use of redo surgery varies depending on the institution. A well-designed randomized controlled trial in this population would help establish the standard of surgical care.

High risk neuroblastoma (HR-NB) with MNA and age &lt;18 months: Results from the HR-NBL1/SIOPEN trial.

10000 Background: The INES 99.4 trial (JCO 2009,27(7):1014-9) for MYCN amplified (MNA) infants using 6 courses of CBDCA-Vp16/CADO showed early progressions or non-response in 30%. Two-year overall survival (OS) was 30% (SE, 0.08) with median survival of 12 months. Aims are to report risk factors and outcomes for patients &lt; 18 months with MNA neuroblastoma treated on HR-NBL1/SIOPEN. Methods: From 2006-2022, patients &lt; 18 months with MNA INSS stages &gt; 1 were eligible. All infants received Rapid Cojec induction, eventually 2 TVDs, Busulfan-Melphalan as high-dose treatment and could receive Dinutuximab- beta immunotherapy. Toddlers (12-18 months) followed the HR-NBL1/SIOPEN respective eligibility criteria. Results: Median age at diagnosis was 1.2 years in 414 patients (median follow up 7 years): 56% were male; 18.6% had localised tumours, 6.8% stage 4S and 75% stage 4. The predominant primary tumour site was abdominal (85%). Rapid Cojec was used in 85%, BUMEL in 89% and 26% received Dinutuximab-beta. Multiple metastatic compartments were reported in 82% of stage 4. Five-year event-free (5y-EFS) and overall survival (5y-OS) was 0.46±0.03 and 0.51±0.03. Stage 2,3&amp;4S patients had a better 5y-EFS of 0.64±0.03 (p &lt; 0.005) (5y-OS:0.66±0.06), compared to stage 4 with 0.41±0.03 (OS:0.46±0.03). Infants’ 5y-EFS was superior with 0.53±0.04 (5y-OS:0.57±0.04) (p = 0.015) over the toddlers with 5y-EFS 0.42±0.03 (5y-OS:0.46±0.03). Patients with bone marrow (BM) and skeletal metastases ± other sites (MS) did worse (p &lt; 0.005) with a 5y-EFS of 0.31±0.04 (5y-OS:0.36±0.04) whilst other metastatic combinations revealed outcomes above 0.50 ±0.03. LDH (2x &gt; normal) predicted a worse 5y-EFS of 0.43±0.03 (5y-OS:0.46±0.03) (p &lt; 0.001) versus normal LDH (5y-EFS 0.71±0.07; 5y-OS:0.80±0.06). EFS multivariable analysis at diagnosis (MVA) showed independent significance for stage 4 (p-value 0.0139; HR: 1.608) and LDH (p-value 0.0042; HR: 2,237), but not for age. In stage 4 patients MVA on EFS found LDH (p-value 0.0098; HR: 2,567) and BM/skeleton involvement (p-value 0.0024; HR: 1,693) as independent risk predictors. In maintenance Dinutuximab-beta had a major impact on 5y-EFS in stage 4 patients with 0.69±0.05(5y-OS:0.71±0.05) vs. 0.41±0-07 (0.46±0.07) for those treated with 13-cis retinoic acid (p = 0.002 &amp; p = 0.001), but not on others. Conclusions: In HR-NBL1/SIOPEN outcomes improved with almost half of patients alive at 5 years and only few late events. Clinical trial information: NCT01704716 .

CtDNA for clonal evolution surveillance and therapeutic efficacy prediction in unresectable locally advanced non-small cell lung cancer under radiotherapy.

e20555 Background: Therapeutic efficacy differs across unresectable locally advanced non-small cell lung cancer (LA-NSCLC) patients receiving definitive radiotherapy/chemoradiotherapy (RT/CRT), but the underlying resistance mechanism, clonal evolution and molecular prognostic factors remain poorly understood. Methods: Unresectable LA-NSCLC patients treated with definitive RT/CRT were consecutively enrolled between May 2018 and November 2020. Next-generation sequencing covering 474 cancer-relevant genes was performed on plasma ctDNA collected at pre-treatment (TP0), 4-week post-RT (TP1), 1-month post-RT (TP2), 3-month post-RT (TP3), and progression (TP4). Main study endpoints included disease progression, progression-free survival (PFS), death from any cause, overall survival (OS), distant metastasis and distant metastasis free survival. Fisher’s exact test and two-sample t-tests were performed to compare the frequencies and means of independent groups, respectively. The median follow-up time was estimated using the reverse Kaplan-Meier method. Hazard ratios (HR) with 95% confidence intervals (CI) were estimated by Cox proportional hazards models. Results: A total of 46 patients were included (median age: 63 [range: 40–80], males: 87%, clinical stage IIIB: 52%, squamous cell carcinoma: 54%, TP0 ctDNA shedding: 63%, consolidation immunotherapy: 33%). Twenty-nine (63%) patients developed disease progression by the end of follow-up (median follow-up: 23.7 months), with median PFS and OS being 15.5 and 25.4 months, respectively. The polymerase epsilon ( POLE) mutational signature at TP0 indicated inferior PFS (HR: 5.32, 95% CI: 1.83–15.45) and worse OS (HR: 20.68, 95% CI: 3.94–108.62). Notably, newly-discovered/lost mutations were rarely observed at TP4 when compared to TP0. Patients with a high ratio of mean over max variant allele frequency (m/mVAF) in TP0 samples, indicative of a clonal predominant tumor with a low subclone fraction ( P&lt; 0.01), had relatively poor OS, compared to patients with low m/mVAF (HR: 2.92, 95% CI: 0.82–10.46) or undetectable ctDNA (HR: 3.39, 95% CI: 0.98–11.75). The prognostic value was validated in an independent publicly available dataset of 431 LA-NSCLC patients receiving definitive RT/CRT, showing patients with high m/mVAF demonstrated worse OS than those with low m/mVAF (HR: 1.43, 95% CI: 1.08–1.89). Additionally, increased m/mVAF between TP0 and TP1 indicated an elevated risk for disease progression ( vs. non-increase, HR: 3.49, 95% CI: 1.20–10.16), especially for distant metastasis ( vs. non-increase, HR: 2.85, 95% CI: 0.84–9.69). Conclusions: Our findings demonstrated the clinical value of plasma ctDNA and its derived molecular features in delineating clonal evolution, monitoring therapeutic resistance, and predicting prognosis of LA-NSCLC under definitive RT.