Tumor Characteristics Research Articles

Depth of invasion threshold for recommending elective neck dissection in T1 or T2 oral squamous cell carcinoma

BackgroundThere is variability in the literature on the role of the depth of invasion (DOI) for recommending an elective neck dissection (END). PurposeThe purpose of the study is to estimate the DOI threshold for recommending an END. Study Design/Setting/SampleA retrospective cohort study was performed at McGill University Health Centre from 2008-2018 with 5 years of follow-up. The sample was subjects with clinical T1/T2 oral squamous cell carcinoma (OSCC) and clinically negative neck. Subjects with previous head and neck cancer were excluded. Predictor VariableThe primary predictor variable was DOI measured from the basement membrane of the adjacent normal mucosa on final pathology, coded as <4mm or ≥4mm. DOI is a continuous variable converted to a binary variable. Main Outcome VariableThe main outcome variable was time to development of neck disease (RD+) defined as the time from surgery to development of pathologic nodes. Time to RD+ for pathologic nodes discovered from the END was considered 0 months. The secondary outcome variable was overall survival. CovariatesDemographics (age, sex, smoking/alcohol history) and tumor characteristics (tumor location, clinical T, tumor differentiation, perineural invasion, lymphovascular invasion) were analyzed. AnalysesTime to RD+ and survival were analyzed using Cox hazard ratio, Kaplan-Meier curves, and log-rank test. Student T-test and Chi-square test were used for bivariate analyses; p≤0.05 was statistically significant. ResultsThe final sample were 64 subjects (average age 65.25 (SD 13.06) years and 36 (56.2%) males). Twenty-nine subjects had DOI<4mm, and the 5-year RD+ was 3.4% (the 1 occurrence of RD+ was at 5.3 months). Thirty-five subjects had DOI≥4mm, and the 5-year RD+ was 45.7% (15 subjects had RD+ discovered from the END, and 1 subject had RD+ at 7.6 months). DOI≥4mm had significantly higher risk of RD+ than DOI<4mm (HR 17.91; 95% CI 2.37-135.3; p=0.01), which remained significant after adjusting for clinical T, tumor differentiation, perineural invasion, and lymphovascular invasion (HR 9.53; 95% CI 1.12-81.44; p<0.05). The shallowest DOI with >20% risk of RD+ was in the DOI 4-4.9mm group. Conclusions/Relevance: Among patients with OSCC of T1 or T2 and clinically negative necks, END should be considered with DOI≥4mm.

Effectiveness of Track Cauterization in Reduction of Adverse Events for Lung Microwave Ablation

PurposeTo evaluate the effectiveness of track cautery for lung microwave ablation (MWA) to reduce post-procedural adverse events (AE). Methods and MaterialsPatients who underwent percutaneous lung MWA between 2012 to 2021 were divided into patients in whom track cautery was conducted during antenna removal and patients in whom the antenna was simply removed. Patient demographics, treatment history, tumor characteristics, and ablation details were collected. Post-procedural AEs including immediate, enlarging, and delayed pneumothorax (PTX), pleural effusion, and reinterventions were recorded. Univariate and multivariate logistic regression models were used to identify factors associated with AEs. ResultsThis study included 365 lung MWA sessions for 190 patients. Of the 165 cautery cohort, 78/165 (47%) had immediate PTX, 16/165 (10%) had enlarging PTX, 2/165 (1%) had delayed PTX, and 15/165 (9%) needed interventions. Of the 200 non-cautery cohort, 85/200 (43%) had immediate PTX, 45/200 (23%) had enlarging PTX, 16/200 (8%) had delayed PTX, and 37/200 (19%) needed interventions. The cautery cohort had significantly reduced rates of enlarging PTX (OR 0.67 [95%CI 0.34-1.33], P=0.002), delayed PTX (OR 0.15 [95%CI 0.03-0.89], P=0.037), and pleural effusion (OR 0.38 [95%CI 0.15-0.99], p=0.049). The presence of emphysema, large tumor size, and left lower lobe location were shown to be significant predictors of AEs and the need for interventions (p<0.05). ConclusionTrack cauterization is associated with reduction of post-MWA enlarging PTX, delayed PTX, and pleural effusion. Presence of emphysema, lack of track cautery, large tumor size, and tumors in the left lower lobe were shown to be predictors of postprocedural AEs.

Multi-center study on sellar reconstruction after endoscopic transsphenoidal pituitary surgery.

Surgical techniques for sellar reconstruction include no reconstruction, use of synthetic materials, autologous grafts, and/or vascularized flaps. The aim of this study was to conduct a multi-center study comparing the efficacy and postoperative morbidity associated with different sellar reconstruction techniques. A retrospective chart review of patients who underwent endoscopic transsphenoidal surgery for pituitary tumors from five participating sites between January 2021 and March 2023 was performed. The variables included demographics, tumor characteristics, reconstruction technique, postoperative cerebrospinal fluid leak (CSF) leak, and 22-item Sino-Nasal Outcome Test (SNOT-22) scores. Comparisons of postoperative complications, SNOT-22 scores, and duration of surgery by type of onlay reconstruction were evaluated using Fisher's exact test, analysis of variance, and Kruskal‒Wallis test. Five hundred and one patients were identified. The median tumor size was 2.1cm, and 64% were non-functioning. Intraoperative CSF leak was identified in 38% of patients. A total of 89% of patients underwent onlay reconstruction: 49% were reconstructed with mucosal grafts, 35% with nasoseptal flaps, and 5% with other onlay techniques. Nasoseptal flaps were utilized more frequently in the setting of giant pituitary adenomas (>3cm), medial cavernous sinus wall resection, and high-flow intraoperative CSF leaks. Cases who utilized mucosal grafts had an overall shorter operating time (median: 183 min vs. 240 min; p<0.001). Five postoperative CSF leaks were identified, and therefore, statistical analysis could not be performed for this complication. The effectiveness and morbidity of different sellar reconstruction techniques are comparable. Vascularized flaps were utilized more frequently in the setting of larger tumors and high-flow intraoperative CSF leaks.

Differentiating primary from metastatic ovarian tumors of gastrointestinal origin by CT

PurposeTo determine differentiating CT imaging features of primary ovarian cancers from ovarian metastases of gastrointestinal origin. MethodsRetrospective study of 50 patients with new ovarian lesions on CT, half were primary ovarian cancers and half gastrointestinal metastases. Two blinded independent readers described tumor characteristics on CT (size, laterality, margin, etc.) and ancillary features (ascites, peritoneal seeding, lymphadenopathy, etc.). Patient age, sex, cancer history, and tumor marker levels for CA-125 and CEA were collected. Wilcoxon test and Pearson's chi-squared test were used for statistical analysis. Results50 patients with mean age of 62.1 years were included. Ovarian metastases were more likely to be cystic/mainly cystic (p=0.013), have smooth margins (p=0.011), and have no/mild enhancement (p<0.001). Primary ovarian lesions were associated with moderate to large volume of ascites (p=0.047) and more commonly seen with lymphadenopathy (p=0.008). Laterality was not significantly different between the two groups. CA-125 level was more commonly elevated in primary ovarian lesions (87% vs 50%, p=0.018), and with much higher values (1076.5 vs 155.1, p=0.013). CEA level was more commonly elevated in metastatic ovarian lesions (83.3% vs 15.4%, p<0.001), and with higher values (72.4 vs 2.1, p<0.001). ConclusionOvarian metastases were more frequently smooth-margined and cystic with little enhancement. Primary ovarian lesions were more commonly associated with lymphadenopathy and larger volume of ascites. Tumor markers CEA and CA-125 were more frequently elevated in metastatic and primary lesions, respectively. Cancer history was the only variable that increased the odds of metastasis and therefore it is important to always correlate with history of cancer.

Robotic Surgery in Paediatric Oncology:Expanding boundaries and defining relevant indications

This article reviews the establishment and progress of the Multidisciplinary Paediatric Robotic Program in a high-volume paediatric surgery department at Hôpital Necker-Enfants Malades, Paris, France. A major foundational principle of the program was to establish a safe and secure environment for patients and staff, both pre-operatively, intra-operatively and post-operatively. This founding principle when applied systematically has allowed increasing confidence across the program and service. The robotic platform allows for precision surgery when approaching tumours, with freedom of movement adapted to meticulous vascular and organ dissection. Surgical feasibility is based on tumour characteristics, pre-operative imaging, with a focus on vascular and organ involvement, considering goals of surgery and surgical experience. Case complexity has been gradually increased (where appropriate) through an iterative process. The future of surgery is robotic, and even more so image-guided surgery, and this synergy has been instrumental when approaching tumour surgery in children. The current principles that guide application of robot-assisted surgery in paediatric tumours are presented. With this blueprint, excellent oncological outcomes can be achieved while utilising a minimally invasive approach in children with selected endocrine, neuroblastic and renal tumours.

Staging accuracy in patients with clinical T2N0 gastric cancer: Implications for treatment sequencing

BackgroundPatients with clinical T2N0 (cT2N0) gastric adenocarcinoma are recommended to undergo either perioperative chemotherapy or upfront resection. If T2N0 disease is pathologically confirmed, patients may be observed without chemotherapy. These guidelines create the possibility of both systemic therapy overuse and underuse depending on clinical staging accuracy. Our objectives were to define factors associated with upstaging after upfront resection and describe the association between postoperative chemotherapy and survival. MethodsPatients with cT2N0 gastric adenocarcinoma were identified using the National Cancer Database. Factors associated with upstaging were assessed by logistic regression. Survival was assessed using Kaplan-Meier and Cox proportional hazard analyses. ResultsOf 4,076 patients undergoing upfront resection for cT2N0 gastric cancer, 1,933 (47.4%) were pathologically upstaged. Patients were more likely to be upstaged if they had >3.0-cm (adjusted odds ratio [aOR] 2.31, 95% confidence interval [CI] 1.97–2.70; P < .001) or poorly differentiated tumors (aOR 2.22, 95% CI 1.89–2.60; P < .001). Patients were less likely to be upstaged if they had distal tumors (aOR 0.77, 95% CI 0.64–0.93; P = .006). Of those pathologically upstaged (n = 1,933), 1,111 (57.4%) received adjuvant chemotherapy that was associated with improved survival (HR 0.55, 95% CI 0.47–0.63; P < .001). Among those not upstaged (n = 2,143), 247 (11.5%) received adjuvant chemotherapy that was not associated with improved survival (HR 0.92, 95% CI 0.70–1.21; P = .54). ConclusionsPathologic upstaging after upfront resection in patients with cT2N0 gastric cancer is associated with patient and tumor characteristics. Adjuvant chemotherapy is associated with improved survival only in the patients upstaged at surgery. An upfront surgical approach may be preferred in select patients, especially if avoiding chemotherapy is desired.

Role of Medical and Surgical Treatment in Management of the Patients With Prolactinoma: A Single-Center Experience.

Current guidelines recommend dopamine agonists (DA) as the primary therapeutic approach for prolactinomas; however, emerging evidence suggests that surgical intervention can also yield favorable outcomes. To comprehensively evaluate prolactinoma patients undergoing surgical and medical treatments at our pituitary center. Retrospective review of mMedical records from prolactinoma patients treated between 2015 and 2022 was performedwere retrospectively reviewed. The study focused on treatment outcomes and remission rates while investigating factors influencing the success of both treatment modalities in achieving remission. A total of 301 prolactinoma patients were included, of whom 199 were women. Among them, 235 were managed medically, while 66 underwent surgical intervention. The overall remission rates of patients treated with medical and surgery were similar at the final examination (Respectively respectively 82.9% and 81.8%, p=0.114). Factors associated with remission in both treatment modalities included female sex, low initial prolactin levels, small adenoma size, and absence of cavernous invasion. Compared to DA treatment, Ssurgical treatment demonstrated a higher rate of drug-free remission compared to DA treatment for microadenomas, and macroadenomas without cavernous invasion. In cases with cavernous invasion, standalone surgical treatment yielded a low rate of drug-free remission (7.7%); however, when combined with DA therapy post-surgery, remission rates increased to 66.7%. Medical treatment with DAs remains the preferred option for macroadenomas with cavernous sinus invasion, and giant adenomas, with surgery reserved for selected cases to address complications. Conversely, surgery emerges as the most effective modality for achieving remission in patients with microadenomas, and macroadenomas confined to the sella. The recommendation of DAs as first-line therapy for all patients has been withdrawn in the current guidelines, and individual treatment approaches based on tumor characteristics are emphasized. Our results support this approach.

Factors associated with delays in receipt of neoadjuvant chemotherapy in patients with operable breast cancer.

126 Background: Delays in neoadjuvant chemotherapy initiation (NACTI) after breast cancer (BC) diagnosis have been associated with worse outcomes. We evaluated incidence and predictors of delays of NACTI among high clinical risk patients treated with NACT on a national level. Methods: We conducted a retrospective cohort study using the National Cancer Database. Eligibility included age ≥18 years, diagnosis of non-metastatic BC between 1/1/2010 – 12/31/2020, who were treated with NACT within 180 days of diagnosis. Patients who received neoadjuvant endocrine therapy were excluded. Time to chemotherapy (TTC) in days was recorded. Patients were categorized into sub-cohorts by receptor status and clinical stage: 1) Hormone Receptor positive/HER-2 negative (HR+/HER2-) and were lymph node (LN) LN+; 2) HER-2 positive (HER2+) cT2+ or LN+; and 3) triple negative BC (TNBC) cT2+ or LN+. Multivariable logistic regression, adjusted for demographic, socioeconomic and tumor characteristics, was used to identify characteristics associated with delays &gt; 60 days from diagnosis to NACTI. Multiple imputation was used for missing data. Results: We identified 145,697 eligible patients, 74% were White, 18% were Black, 3.3% were Asian, and 4.6% were Other/Unknown. Across all racial categories, 9.2% were Hispanic. Median age at diagnosis was 52 years (range 18-90), median TTC was 32 days (range 0-180), and 10% had a delay &gt; 60 days. There were 40,345 patients in the HR+/HER2- cohort, 56,868 in the HER2+ cohort, and 48,484 in the TNBC cohort; 12%, 9.0%, and 8.9% (p &lt; 0.001) had a delay in NACTI, respectively. In multivariable analysis among the HR+/HER2- sub-cohort, characteristics associated with delays in NACTI included Black race (OR 1.71, 95%CI 1.57-1.86) and Hispanic ethnicity (OR 1.76, 95%CI 1.60-1.94) compared to White and non-Hispanic patients. Patients with Medicare, Medicaid, or who were uninsured were more likely to be delayed (OR 1.44 95%CI 1.30-1.58, 2.10, 95%CI 1.92-2.29, 2.28, 95%CI 1.99-2.61) compared to those with commercial insurance. Results were similar in the HER2+and TNBC cohorts, as seen (Table). Conclusions: Among patients with operable BC who received NACT, patients who were Black, Hispanic, had Medicaid or no insurance had as high as a twofold increase in odds of a delay in NACTI. Targeted interventions to address these racial and socioeconomic disparities are necessary to ensure equitable care. Multivariable logistic regression adjusted for demographic, socioeconomic, and tumor characteristics variables (n = 145,697). HR+/HER2-N= 40,345 HER2+N= 56,868 TNBCN= 48,484 OR 95%CI OR 95%CI OR 95%CI Black Race 1.71 1.57-1.86 1.89 1.74-2.04 1.90 1.76-2.06 Hispanic Ethnicity 1.76 1.60-1.94 2.18 2.00-2.36 2.00 1.80-2.21 Medicare 1.44 1.30-1.58 1.46 1.34-1.61 1.45 1.32-1.61 Medicaid 2.10 1.92-2.29 2.13 1.96-2.31 2.14 1.96-2.34 No Insurance 2.28 1.99-2.61 2.36 2.07-2.70 2.25 1.96-2.59

Optimal Sequence for Total Neoadjuvant Therapy in Locally Advanced Rectal Cancer: An Evidence-Based Review.

Historically, multimodal therapeutic strategies involving preoperative chemoradiotherapy (CRT), surgery, and adjuvant chemotherapy (CT) have been employed to treat locally advanced rectal cancer (LARC). Total Neoadjuvant Therapy (TNT) is showing promise in improving outcomes. Despite its benefits, the optimal sequencing within TNT-whether induction chemotherapy should precede or follow chemoradiotherapy-remains a critical question. This study endeavors to explore the effects of different TNT sequencing strategies on patient outcomes, including tumor downstaging, pathological response, organ preservation, and the balance between efficacy and tolerability. Our methodology entailed a comprehensive literature review conducted on Medline, focusing on recent research, including retrospective studies, systematic reviews, and clinical trials. The review emphasized the comparison of induction chemotherapy versus consolidation chemotherapy within TNT regimens, assessing outcomes such as pathological response, organ preservation rates, and adverse effects. To ensure the selection of appropriate and high-quality studies, specific inclusion and exclusion criteria were applied. The analysis revealed that induction chemotherapy might lead to decreased adherence to subsequent chemoradiotherapy while offering an early intervention against micrometastasis and potentially improving overall chemotherapy compliance. Conversely, consolidation chemotherapy has been associated with higher pathological complete response (pCR) rates and improved tolerability, indicating its potential for patients requiring local symptom relief or those eligible for a nonoperative management approach. Comparative studies like CAO/ARO/AIO-12 and the OPRA trials have significantly contributed to our understanding, suggesting that while both strategies have distinct advantages, the choice between induction and consolidation chemotherapy should be tailored based on individual patient profiles and tumor characteristics. This narrative review underscores the importance of a nuanced approach to TNT sequencing in locally advanced rectal cancer, highlighting the need for further research to refine treatment strategies.

Grading carcinoembryonic antigen levels can enhance the effectiveness of prognostic stratification in patients with colorectal cancer: a single-centre retrospective study.

This study developed a refined carcinoembryonic antigen (CEA) grading system using CEA cut-off points of 5, 20 and 50 ng/mL and to explore the prognostic value of CEA grading in predicting the progression-free survival (PFS) and overall survival (OS) of colorectal cancer (CRC) patients. A retrospective cohort study. First Affiliated Hospital of Guangxi Medical University. 1107 CRC patients who received surgical treatment. Survival analysis was conducted using the Kaplan-Meier method and compared using the log-rank test. A Cox regression model with a 95% CI was used to evaluate the independent prognostic risk factors for CRC. Prognostic nomograms were constructed to predict the 1-5-year PFS/OS. Elevated serum CEA levels are often indicative of recurrence and death in CRC patients. Higher CEA levels were significantly associated with more aggressive tumour phenotypes. The CEA grading system was an independent predictor of prognosis in CRC patients and effectively stratified PFS (62.0% vs 51.2% vs 33.7% vs 20.2%, p<0.001) and OS (64.7% vs 54.4% vs 36.6% vs 22.5%, p<0.001) in CRC patients. As the CEA grade increased, the risk of poor prognosis gradually increased in a gradient manner, with an approximately 10% difference in risk grade between each CEA grade. The internal validation cohort further confirmed that CEA grade remains an effective prognostic factor for the survival of CRC patients. Prognostic nomograms, which integrate individual characteristics, tumour features and CEA grading, provide a more comprehensive prognostic evaluation for CRC patients. The CEA grading system is an independent predictor of prognosis for CRC patients and can effectively stratify PFS and OS.

EP.14C.10 Clinical and Pathoanatomical Characteristics of Rare Pulmonary Neuroendocrine Tumors in Greek Population

EP.14C.10 Clinical and Pathoanatomical Characteristics of Rare Pulmonary Neuroendocrine Tumors in Greek Population

Brain Metastases from Esophageal Cancer: A Retrospective Review from a Single Institution

Patients with brain metastases (BrM) from esophageal cancer have poor prognosis, the incidence of which is expected to rise due to improved survival from the primary tumor and increased neuroimaging. We aimed to identify patient and esophageal cancer characteristics associated with shorter survival in patients with BrM and, secondly, to compare the prognosis of patients with HER2 overexpression. We retrospectively reviewed patients with BrM from esophageal cancer at a single institution from 2008-2021. We collected patient demographics, primary tumor and BrM characteristics, and treatment. Our primary outcome was median survival from the time of BrM. The median age at primary diagnosis was 66.5 years and 86% were male. Of the 49 patients, 71% had adenocarcinoma, 20% squamous cell carcinoma and 8% other. 71% of patients presented with stage III or IV disease, including 16% with synchronous primary and BrM. The median time to BrM was 10.1 months (IQR 1.7-22.8) and the median survival from BrM was 8.4 months (95%CI 4.8-16.8). On multivariable analysis, treatment with stereotactic radiosurgery (HR=0.19;p=0.04), surgical resection (HR 0.24;p=0.03) and immunotherapy (HR 0.19;p=0.04) were associated with increased survival while KPS ≤70 (HR=13.2;p<0.001) was associated with decreased survival. HER2 overexpression was found in 22% of patients, but we noted no survival difference (5.2 months HER2+ versus 9.8 months HER2neg;p=0.95). The median survival from esophageal-to-brain metastasis was 8.4 months. Patients with a single lesion, KPS score >70, and treatment with surgical resection was correlated with improved survival. Further, HER2+ patients had distinct patient and BrM characteristics.

Residual Nodal Burden After Neoadjuvant Chemotherapy in cN1 Breast Cancer Patients with Positive Nodes at Targeted Axillary Dissection.

Targeted axillary dissection (TAD) facilitates nodal staging in cN1 breast cancer after neoadjuvant chemotherapy (NAC). Completion axillary node dissection (cALND) remains the standard of care for TAD-positive patients. This study investigated factors associated with additional positive nodes at cALND (cALND+) and the impact on the residual cancer burden (RCB). Retrospective review of cN1 breast cancer patients treated with NAC and TAD was conducted from July 2013 to June 2023. The review defined cN1 status by ultrasound (US) and biopsy. Patient, tumor, and treatment characteristics were evaluated. Multivariate analysis was performed to identify factors associated with cALND+, and RCB was calculated. Of 902 patients who underwent TAD, 554 (61.4%) were TAD-positive. 457 underwent cALND, and 124 (27%) were cALND+ (average 4.1 additional +nodes). The cALND+ patients had larger primary tumors at diagnosis (4 vs 3.5 cm; p=0.04), more than three suspicious nodes on initial US (30% vs 13%; p≤0.0001), larger residual primary tumors on pathology (median, 3 vs 2.1 cm; p=0.0004), and more positive TAD nodes (median, 2 vs 1; p≤0.0001). In the multivariate analysis, the factors associated with cALND+ were more than three suspicious nodes on initial US (odds ratio [OR], 2.9; p≤0.0001), more positive TAD nodes (OR, 1.1; p≤0.0001), larger clipped node metastasis (OR, 1.1; p≤0.0001), and larger residual tumor on pathology (OR, 1.1; p=0.006). Of 65 cALND+ patients with RCB class I or II, 29 (45%) had an increase in RCB based on cALND. Of cN1 breast cancer patients treated with NAC who are TAD-positive, approximately 25% will have additional nodal disease on cALND. In these patients, positive cALND is associated with greater disease burden, which has potential implications for RCB status and prognosis.

Spatial resolution of the head and neck cancer tumor microenvironment to identify tumor and stromal features associated with therapy response.

Head and neck cancer (HNC) is the seventh most common cancer globally, resulting in 440 000 deaths per year. While there have been advancements in chemoradiotherapy and surgery, relapse occurs in more than half of HNCs, and these patients have a median survival of 10 months and a 2-year survival of < 20%. Only a subset of patients displays durable benefits from immunotherapies in metastatic and recurrent HNC, making it critical to understand the tumor microenvironment (TME) underpinning therapy responses in HNC. To recognize biological differences within the TME that may be predictive of immunotherapy response, we applied cutting-edge geospatial whole-transcriptome profiling (NanoString GeoMx Digital Spatial Profiler) and spatial proteomics profiling (Akoya PhenoCycler-Fusion) on a tumor microarray consisting of 25 cores from 12 patients that included 4 immunotherapy-unresponsive (8 cores) and 2 immunotherapy-responsive patients (5 cores), as well as 6 immunotherapy naïve patients (12 cores). Through high-plex, regional-based transcriptomic mapping of the tumor and TME, pathways involved with the complement system and hypoxia were identified to be differentially expressed in patients who went on to experience a poor immunotherapy response. Single-cell, targeted proteomic analysis found that immune cell infiltration of the cancer cell mass and interactions of CD8 Tcells with tumor and other immune cells were associated with positive immunotherapy response. The relative abundance of specific tumor phenotypes and their interactions with various immune cells was identified to be different between response groups. This study demonstrates how spatial transcriptomics and proteomics can resolve novel alterations in the TME of HNC that may contribute to therapy sensitivity and resistance.

Clinicopathological, molecular, and prognostic features of colorectal carcinomas with KRAS c.34G>T (p.G12C) mutation.

Evidence indicates that combinations of anti-EGFR antibodies and KRAS p.G12C (c.34G>T) inhibitors can be an effective treatment strategy for advanced colorectal cancer. We hypothesized that KRAS c.34G>T (p.G12C)-mutated colorectal carcinoma might be a distinct tumor subtype. We utilized a prospective cohort incident tumor biobank (including 1347 colorectal carcinomas) and detected KRAS c.34G>T (p.G12C) mutation in 43 cases (3.2%) and other KRAS mutations (in codon 12, 13, 61, or 146) in 467 cases (35%). The CpG island methylator phenotype (CIMP)-low prevalence was similarly higher in KRAS c.34G>T mutants (52%) and other KRAS mutants (49%) than in KRAS-wild-type tumors (31%). KRAS c.34G>T mutants showed higher CIMP-high prevalence (14%) and lower CIMP-negative prevalence (33%) compared with other KRAS mutants (6% and 45%, respectively; p = 0.0036). Similar to other KRAS mutants, KRAS c.34G>T-mutated tumors were associated with cecal location, non-microsatellite instability (MSI)-high status, BRAF wild type, and PIK3CA mutation when compared with KRAS-wild-type tumors. Compared with BRAF-mutated tumors, KRAS c.34G>T mutants showed more frequent LINE-1 hypomethylation, a biomarker for early-onset colorectal carcinoma. KRAS c.34G>T mutants were not associated with other features, including the tumor tissue abundance of Fusobacterium nucleatum (F. animalis), pks+ Escherichia coli, Bifidobacterium, or (enterotoxigenic) Bacteroides fragilis. Among 1122 BRAF-wild-type colorectal carcinomas, compared with KRAS-wild-type tumors, multivariable-adjusted colorectal cancer-specific mortality hazard ratios (95% confidence interval) were 1.82 (1.05-3.17) in KRAS c.34G>T (p.G12C)-mutated tumors (p = 0.035) and 1.57 (1.22-2.02) in other KRAS-mutated tumors (p = 0.0004). Our study provides novel evidence for clinical and tumor characteristics of KRAS c.34G>T (p.G12C)-mutated colorectal carcinoma.

Prospective selective embedding of radical prostatectomy specimens is not inferior to full embedding regarding established and new prognostic parameters.

The histopathological examination of radical prostatectomy specimens is essential for assessing critical tumor characteristics, including stage, grade, and margins, all of which impact patient prognosis. However, the extent of embedding the prostate has long been a subject of debate, with some advocating partial/selective embedding and others favoring complete embedding. This study establishes a standardized and time-efficient protocol for processing radical prostatectomy specimens with limited embedding while maintaining diagnostic accuracy. Two hundred twenty-six prostatectomy specimens were analyzed, and the results of a highly standardized selective embedding protocol, systematically embedding the apex, the base, the transition to the seminal vesicles, and selected horizontal sections, were compared with full embedding as the gold standard. Non-inferiority testing was conducted by one-sided binomial tests and Pearson-Clopper confidence intervals. Selective embedding provided consistent and accurate diagnostic information with up to 90-98% concordance in pT, margins, ISUP-grade groups, and presence of IDC-P and cribriform tumor growth. In summary, this study establishes an economical standardized protocol for selective embedding of radical prostatectomy specimens with only minimal loss of information.

Hexokinase 2 as an independent risk factor for worse patient survival in esophageal adenocarcinoma and as a potential therapeutic target protein: A retrospective, single‑center cohort study.

Cancer cells exhibit a distinct metabolic profile that features an upregulation of less efficient glycolysis accompanied by lactate production for energy generation, in contract to the characteristic metabolism of normal cells. Consequently, cancer research has focused on the enzymes that participate in these cancer metabolic pathways. Among them, hexokinase 2 (HK2) has an important position as the initial enzyme in the glycolytic pathway. Increased expression levels of HK2 have been correlated with an increased risk of poor patient outcomes and advanced tumor stages in a number of malignant tumors, such as gastric carcinoma. The present study aimed to investigate the specific role of HK2 in patients diagnosed with esophageal adenocarcinoma. A total of 643 patients with esophageal adenocarcinoma were included. Immunohistochemical staining and HK2 mRNA in situ probes were used to investigate the association of HK2 expression levels with clinical and molecular tumor characteristics. Patients who exhibited high HK2 expression levels demonstrated significantly reduced overall survival (OS) times compared with patients who exhibited low HK2 expression levels (29.6 vs. 39.9 months, respectively; P=0.027). Furthermore, high HK2 expression levels were demonstrated to be an independent risk factor for reduced patient survival (hazard ratio, 1.65; 95% CI, 1.09-2.50; P=0.018). Significantly reduced patient survival was also demonstrated in the subgroups of male patients, patients with primarily resected tumors, patients with HER2-negative tumors and patients with tumors exhibiting Y chromosome loss. Elevated expression of HK2 was identified as a risk factor for unfavorable patient survival in esophageal adenocarcinoma. This revelation suggests the potential for future diagnostic and therapeutic avenues tailored to this specific patient subset. Identifying patients with high HK2 expression may pinpoint a higher-risk cohort, paving the way for comprehensive prospective studies that could advocate for intensified monitoring and more aggressive therapeutic regimens. Furthermore, the targeted inhibition of HK2 could hold promise as a strategy to potentially enhance patient outcomes.

Assessing the long-term prognostic ability of the 70 gene expression signature MammaPrint in an Italian single-center prospective cohort study of early-stage intermediate-risk breast cancer patients

PurposeThe aim of this study was to assess the prognostic performance of the 70-gene signature, MammaPrint, in an Italian single-center prospective cohort of early-stage intermediate-risk breast cancer (BC) patients. MethodsA total of 195 eligible early BC cases were tested for genomic risk between 2006 – 2013. In this retrospective analysis, the association of genomic risk with distant metastasis-free survival (DMFS) and overall survival (OS) were assessed using Cox regression models, adjusting for clinical and pathological tumor characteristics. ResultsMammaPrint identified 118 (60.5%) patients with genomically Low Risk tumors and 77 (39.5%) patients with genomically High Risk tumors. Age, menopausal status, tumor size, receptor status, and nodal status were comparable between MammaPrint Risk categories. The median follow-up was 8.4 years for DMFS and 9.3 years for OS; 8-year follow-up was reported for both endpoints. The 8-year DMFS was 90.4% (95% CI 84.9 – 95.9) in patients with MammaPrint Low Risk tumors compared to 60.8% (95% CI 49.8 – 71.8) for patients with High Risk tumors. Patients with MammaPrint Low Risk tumors exhibited significantly superior 8-year OS (97.3%; 95% CI 94.4 – 100) compared with MammaPrint High Risk tumors (89.5%; 95% CI 82.6 – 96.4; p = 0.028). Multivariate analyses identified MammaPrint as significantly associated with 8-year DMFS and MammaPrint together with Progesterone Receptor positivity with 8-year OS. ConclusionThe prognostic performance of MammaPrint was demonstrated in early-stage clinically intermediate to high-risk BC patients. Moreover, patients with MammaPrint Low Risk tumors had good outcome regardless of treatment regimen, thus supporting personalized treatment choices.

Exploring the Impact of Model Complexity on Laryngeal Cancer Detection.

Background: Laryngeal cancer accounts for a third of all head and neck malignancies, necessitating timely detection for effective treatment and enhanced patient outcomes. Machine learning shows promise in medical diagnostics, but the impact of model complexity on diagnostic efficacy in laryngeal cancer detection can be ambiguous. Methods: In this study, we examine the relationship between model sophistication and diagnostic efficacy by evaluating three approaches: Logistic Regression, a small neural network with 4 layers of neurons and a more complex convolutional neural network with 50 layers and examine their efficacy on laryngeal cancer detection on computed tomography images. Results: Logistic regression achieved 82.5% accuracy. The 4-Layer NN reached 87.2% accuracy, while ResNet-50, a deep learning architecture, achieved the highest accuracy at 92.6%. Its deep learning capabilities excelled in discerning fine-grained CT image features. Conclusion: Our study highlights the choices involved in selecting a laryngeal cancer detection model. Logistic regression is interpretable but may struggle with complex patterns. The 4-Layer NN balances complexity and accuracy. ResNet-50 excels in image classification but demands resources. This research advances understanding affect machine learning model complexity could have on learning features of laryngeal tumor features in contrast CT images for purposes of disease prediction.

A new nano approach to prevent tumor growth in the local treatment of glioblastoma: Temozolomide and rutin-loaded hybrid layered composite nanofiber

Total resection of glioblastoma (GB) tumors is nearly impossible, and systemic administration of temozolomide (TMZ) is often inadequate. This study presents a hybrid layered composite nanofiber mesh (LHN) designed for localized treatment in GB tumor bed. The LHN, consisting of polyvinyl alcohol and core-shell polylactic acid layers, was loaded with TMZ and rutin. In vitro analysis revealed that LHN™Z and LHNrutin decelerated epithelial-mesenchymal transition and growth of stem-like cells, while the combination, LHN™Z+rutin, significantly reduced sphere size compared to untreated and LHN™Z-treated cells (P < 0.0001). In an orthotopic C6-induced GB rat model, LHN™Z+rutin therapy demonstrated a more pronounced tumor-reducing effect than LHN™Z alone. Tumor volume, assessed by magnetic resonance imaging, was significantly reduced in LHN™Z+rutin-treated rats compared to untreated controls. Structural changes in tumor mitochondria, reduced membrane potential, and decreased PARP expression indicated the activation of apoptotic pathways in tumor cells, which was further confirmed by a reduction in PHH3, indicating decreased mitotic activity of tumor cells. Additionally, the local application of LHNs in the GB model mitigated aggressive tumor features without causing local tissue inflammation or adverse systemic effects. This was evidenced by a decrease in the angiogenesis marker CD31, the absence of inflammation or necrosis in H&E staining of the cerebellum, increased production of IFN-γ, decreased levels of interleukin (IL)-4 in splenic T cells, and lower serum AST levels. Our findings collectively indicate that LHN™Z+rutin is a promising biocompatible model for the local treatment of GB.