T1 Tumors Research Articles

The Many Faces of Myxopapillary Ependymomas.

Myxopapillary ependymomas (MPEs), classified as grade 2 tumors by the World Health Organization, are rare spinal neoplasms. Despite their slow growth and generally benign nature, MPEs have a high recurrence rate and potential for CSF dissemination. This study aims to identify the MRI characteristics and pathologic patterns of MPE and investigate potential correlations between the MRI characteristics and specific histopathologic patterns. We assessed 13 patients (7 men; mean age, 45.1 years) with pathologically proved MPE. MR images were reviewed for tumor location, size, T1 and T2 signal characteristics, contrast enhancement, hemosiderin cap presence, vertebral scalloping, drop metastasis, and prominent intradural flow voids. Four histopathologic patterns (microcystic, solid, hemorrhagic, and high hyalin content) were defined and segmented, with surface areas measured and percentages calculated relative to the total tissue surface. Most tumors were in the lumbar region (84.61%), with MRI revealing typical features such as T2 hyperintensity (100%) and contrast enhancement (92.3%). A rare nonenhancing MPE was noted. Large tumors exhibited a microcystic pathology pattern, with 2 cases with this pattern showing drop metastasis on MRI. Smaller tumors typically presented a solid pathology pattern with homogeneous MRI signals. This study underscores the diverse MRI presentations of MPE and suggests a potential link between microcystic patterns in pathology and large MPE with drop metastasis.

Clinical and molecular characterization of FAP and SPP1 in colorectal cancer (CRC), CALGB (Alliance)/SWOG 80405 and real-world data.

276 Background: FAP and SPP1 contribute to immune modulation in the CRC tumor microenvironment (TME). FAP is expressed by cancer associated fibroblasts, aiding in tissue remodeling and tumor invasion. SPP1 is an integrin-binding protein expressed by tumor associated macrophages that promotes tumor growth, adhesion, and metastasis. We present a clinical and molecular characterization of FAP and SPP1 in CRC. Methods: We analyzed 24,257 CRC samples tested at Caris Life Sciences (Phoenix, AZ) with WTS (Illumina NovaSeq), NextGen DNA sequencing (NextSeq), and PD-L1 expression (SP142, positive ≥ 2+, 5%). RNA deconvolution analysis estimated cell infiltration in the TME. Data from the phase 3 CALGB/SWOG 80405 trial (NCT00265850) on 433 metastatic CRC patients treated with bevacizumab (Bev, n = 226) or cetuximab (Cet, n = 207) in combination with first-line chemotherapy were also evaluated. RNA isolated from FFPE tumor samples were sequenced with HiSeq 2500 (Illumina). Overall survival (OS) and progression-free survival (PFS) were compared using Cox regression in categorical gene expression tertiles (high (T3), medium (T2), and low (T1)) for FAP and SPP1 . Results: FAP -T3 and SPP1 -T3 had increased PD-L1 positivity (q<0.05), while SPP1 -T3 also demonstrated increased MSI-H (8.4% vs 5.3%) and TMB-H(>10 mt/mb, 15.0% vs 10.1%) status relative SPP1 -T1 (all q<0.001). T3 of both genes of correlated with increased M1/M2 macrophages, NK cells and T cell inflamed score (q<0.001); dendritic cells and neutrophils were increased in SPP1 -T3 and FAP -T1 tumors (q<0.05). FAP -T3 and SPP1 -T3 had increased pathway activation of epithelial-mesenchymal transition (EMT), inflammatory response, TNF-a signaling, angiogenesis and KRAS signaling (all q < .005). In Caris cohorts, FAP -T3 demonstrated worse OS in Cet/panitumumab treated CRC (T3: 23.6 vs T1: 21.0 months [mo], P = .005; HR 0.85, 95% CI [0.77-0.95]), but SPP1 did not correlate with OS. In 80405, FAP -T3 showed shorter PFS (T3: 9.5 vs T2: 11.5 vs T1: 12.6 mo, T3 vs T1 (reference) adjusted HR 1.27 [1.07-1.51]) and OS (25.2 vs 29.4 vs 35.5 mo, adjusted HR 1.31 [1.10-1.57]). Similarly, SPP1 -T3 demonstrated worse PFS (9.0 vs 12.7 vs 14.0 mo, adjusted HR 1.29 [1.12-1.48]) and OS (20.9 vs 34.0 vs 36.3 mo, HR 1.24 [1.07-1.44], P < 0.001). Treatment interaction tests noted FAP -T1 CRC benefited from Cet over Bev with respect to PFS ( P = 0.003) and OS ( P = 0.044), while SPP1-T1 tumors demonstrated a PFS benefit with Cet ( P = 0.009). Conclusions: Our results indicate that increased FAP and SPP1 expression is associated with immune cell infiltration, EMT, and inflammatory signaling. Additionally, their expression may be prognostic and predictive of targeted therapy. These data support the evaluation of FAP and SPP1 as predictive markers and therapeutic targets in CRC.

Utility of computed tomography (CT) –based staging of mismatch repair deficient (dMMR) colon cancer.

45 Background: dMMR tumors are characterized by rapid primary tumor growth with reduced likelihood for nodal and distant metastases compared to MMR proficient (pMMR) tumors. Neoadjuvant immune checkpoint inhibitors (ICIs) have demonstrated promising efficacy for localized colon cancer with high pathologic complete response rates and low relapse rates. This raises the question if surgical treatment could be avoided with accurate radiographic staging while avoiding overtreatment of early stage tumors. This study assesses the utility of radiographic staging by CT for dMMR tumors compared to pathologic staging. Methods: Patients with stage I-III colon cancer treated with upfront surgical resection were retrospectively reviewed from a single institution from 2012 to 2023 in two cohorts: 1) dMMR colon cancer and 2) pMMR colon cancer limited to similar sample size as matched controls. Clinical stage was determined based on CT scans prior to surgical resection by 2 independent radiologists blinded to pathologic stage, and the results were correlated to pathologic stage. Clinical characteristics were extracted from the electronic medical record. Statistical analysis was performed using SPSS. Results: We identified 80 patients with dMMR colon cancer and 66 with pMMR tumors. CT clinical tumor staging was discordant from pathologic staging for 68% of dMMR tumors and 61% for pMMR tumors. For T4 dMMR tumors, CT had a 74% sensitivity and 44% specificity. T4 tumors were understaged by radiology to less than T4 for 56% of cases. For dMMR nodal staging, CT had 89% sensitivity and 50% specificity (Table 1). For pathologic node positive tumors, 14% were understaged by radiologist CT read to node negative. For pathologic node negative tumors, 50% of tumors were overstaged to node positive by radiologist CT read. There was poor inter-rater reliability for both T stage and N stage for dMMR and pMMR tumors. The weakest agreement between radiologists was for T stage (dMMR kappa = 0.246, mMMR kappa = 0.145). Conclusions: Radiologic clinical staging of dMMR and pMMR colon cancer does not correlate well with pathologic staging. There were high rates of understaging by CT evaluation for patients who may be candidates for neoadjuvant treatment (T4, N+). Furthermore, there was poor inter-rater reliability between radiologists, indicating that CT staging alone may not be sufficient. Additional diagnostic modalities for nodal detection may be necessary to accurately clinically stage patients before neoadjuvant ICIs in patients with locally advanced disease. Comparing utility of pMMR versus dMMR tumors for T4 and node positive disease. pMMR (n = 66) dMMR (n = 80) T4 versus T3 or less Sensitivity (%) 92 74 Specificity (%) 51 47 PPV (%) 80 77 NPV (%) 82 63 Node positive versus node negative Sensitivity (%) 60 50 Specificity (%) 75 89 PPV (%) 81 89 NPV (%) 53 50 Abbreviations: PPV = positive predictive value; NPV = negative predictive value.

Disparities in organ preservation rate for high-risk stage I rectal cancer.

37 Background: Guidelines for the treatment of high-risk stage I rectal cancer is a curative oncologic resection, while recommendations for stage II/III rectal cancer include neoadjuvant therapy with the option for organ preservation. The paradoxical nature of treating less advanced stage cancer with more morbid surgery calls into question the use of organ preservation strategies (OP) for less advanced disease. While sphincter preservation is appealing, benefits from OP require commitment to preoperative therapy, which may require more significant time and financial commitments than a single-stage curative treatment. This study aims to evaluate disparities in social determinants of health regarding receipt of OP compared to major oncologic resection for high-risk stage I rectal cancer. Methods: The National Cancer Database was queried to analyze all patients with high-risk stage 1 rectal cancer between 2004-2021. High-risk stage 1 disease was defined as either T2 or T1 tumors with lymphovascular invasion, or grade 3 or 4 differentiation. Covariates in patients who underwent OP, defined as chemoradiation therapy without oncologic resection or local excision, were compared to those who underwent major oncologic resection. Additional variables included age, sex, race, great circle distance, insurance status, education, facility type, income, rurality, and comorbidity index. Univariate and multivariate analyses were utilized to compare association of covariates to OP. Results: Of the 63,762 patients included, 9,261 (14.5%) underwent OP. Increased rates of OP were seen with increasing age (OR 1.029, p<0.0001), female sex (OR 1.147, p<0.0001), higher education level (OR 1.179, p=0.0034), rurality (OR 1.273, p=0.0003) and lower income (OR 0.757 for income >74K, p <0.0001). Interestingly, OP was more frequently utilized at community cancer centers in comparison to comprehensive cancer centers (OR 0.78, p<0.0001) and academic centers (OR 0.842, p=0.0021). Race, insurance status, distance to treatment, and comorbidity index were not statistically significant predictors of OP. Of note, those who underwent OP had a considerable delay in time to first treatment, with median time to treatment of 36 days in comparison to 13 days for oncologic resection. Conclusions: Socioeconomic and demographic variables are associated with receipt of OP. While plausible that a treatment strategy that requires frequent office visits, travel expenses, and time off from work may preclude OP, lower income and rurality had increased odds of OP. Future aims should be directed to identifying root causes of disparities in treatment and their clinical consequences.

Diagnostic and prognostic relevance of inflammatory markers in surgically treated thymic epithelial tumors: An international multicenter study.

Complementary prognostic markers are needed in thymic epithelial tumors (TETs) to aid patient stratification and determine the most appropriate follow-up strategies. This study aimed to assess the diagnostic and prognostic relevance of blood-based inflammatory markers in a large cohort of surgically treated TET patients. A total of 743 TET patients who underwent surgical resection between 1999-2021 were included in this multicenter study. Inflammatory markers were recorded from the most recent preoperative blood cell count prior to surgery. Measured variables were rescaled and harmonized to obtain comparable values across the participating centers. Preoperative CRP was significantly higher in TET patients with increased tumor size (vs. those with T1 tumors, p=0.035). Likewise, neutrophil-to-lymphocyte ratio (NLR) (p=0.002) and platelet-to-lymphocyte ratio (PLR) (p<0.001) were both significantly higher in thymic carcinomas than in thymomas. Notably, increased NLR and PLR were mainly attributed to significantly decreased lymphocyte levels in thymic carcinoma patients. Concerning survival outcomes, we found that elevated PLR and fibrinogen influenced overall survival (OS) (p=0.002 and p=0.018, respectively) and cause-specific survival (CSS) (p=0.002 and p=0.009, respectively) independently of other variables in our multivariate models, and they constituted negative prognosticators in TETs. Elevated CRP had an independent negative impact only on OS. Although elevated NLR was linked with impaired prognosis in our univariate model (p=0.008), its independent prognostic significance could not be validated. Using the so-far largest cohort of surgically treated TET patients, our study demonstrates that CRP, PLR, and NLR have diagnostic significance in TETs, while elevated PLR and fibrinogen constitute independent negative prognosticators for OS and CSS. Accordingly, the current multicenter study offers additional guidance in developing personalized surveillance protocols in thymoma and thymic carcinoma.

Predictive value of Bladder EpiCheck® in detecting residual tumor before second TUR for non-muscle-invasive bladder cancer.

As Bladder EpiCheck® (BE) is a promising urinary biomarker for diagnosis and follow up of non-muscle-invasive bladder cancer (NMIBC), there are no studies evaluated this tool for second transurethral resection (TUR) indication. We aim to evaluate the performance of BE in predicting residual tumor before second TUR in NMIBC and its effects on clinical decision making. A total of 50 patients who were diagnosed with NMIBC and indicated for a second TUR were included in the study prospectively. The urine sample taken one day before the second TUR operation was evaluated with BE and the results were compared with second TUR pathologies. The mean age was 65.3 and 45 of the patients were male. Specificity and negative predictive value of BE in primary tumor stage Ta were 100% and 87.5% while in primary tumor stage T1 were 71.4% and 68.2%, respectively. The specificity and negative predictive value of BE were 77.8% and 75%, respectively, in patients with high grade primary tumor. When all NMIBC were evaluated, the specificity and negative predictive value of BE were found to be 78.6% and 73.3% for second TUR, respectively. As an independent predictor of residual tumor in this group, positivity rates of BE were higher in T1 (p < 0.037) and high grade (p < 0.002) tumors. BE may be useful in detecting residual tumor before second TUR and benefit in clinical decision making with high specificity and negative predictive value. These results encourage the use of BE to reduce number of unnecessary second TUR procedures. It may improve cost effectivity and quality of life as high numbered studies are needed to support these views and to incorporate BE into clinical practice.

Large Unstained Cells: A Predictive Biomarker for Recurrence and Survival in Resected Gastric Cancer

Background and Objectives: Despite advances in surgery and perioperative chemotherapy, locally advanced gastric cancer continues to pose significant challenges, creating a pressing need for biomarkers capable of predicting therapeutic efficacy and survival outcomes. This study evaluates the prognostic and predictive significance of large unstained cells (LUCs), a morphologically distinct subset of white blood cells identified in peripheral blood that remain unstained by standard hematological dyes, as potential indicators of immune competence and treatment response. Materials and Methods: This retrospective analysis included patients diagnosed with locally advanced gastric cancer (cT2-4, N0-3) at Ankara Bilkent City Hospital between January 2018 and November 2024. Primary endpoints were overall survival (OS) and disease-free survival (DFS), stratified by LUC levels. The secondary endpoint was the association between LUC levels and pathological tumor response. Results: A total of 180 patients were analyzed, with a median age of 59 years; a total of 76% were male. The median follow-up period was 16.5 months, during which OS and DFS rates were 82% and 66%, respectively. Most patients were presented with advanced-stage disease, including T3–T4 tumors (91%) and nodal positivity (81%). Stratification by LUC levels revealed significantly shorter DFS (HR: 2.12; 95% CI: 1.12–4.01; p = 0.020) and OS (HR: 3.37; 95% CI: 1.26–9.03; p = 0.015) in the low-LUC group compared to the high-LUC group. Furthermore, the high-LUC group exhibited a significantly higher tumor shrinkage rate (ypN0: 60% vs. 44%; p = 0.020), although tumor regression scores were similar across groups. Advanced tumor stage and lack of pathological response were strongly associated with reduced DFS and OS, while poorly cohesive carcinoma histology emerged as a predictor of inferior OS. Conclusions: This study demonstrates that elevated LUC levels are significantly associated with improved DFS and OS, as well as enhanced tumor shrinkage, in patients with locally advanced gastric cancer. These findings show the potential of LUCs as a promising biomarker for prognostication and therapeutic stratification in this population, offering a novel avenue for refining clinical decision-making. Further validation through prospective investigations is warranted.

Robust circulating microRNA signature for the diagnosis and early detection of pancreatobiliary cancer

BackgroundA new circulating biomarker superior to carbohydrate antigen 19–9 (CA19-9) is needed for diagnosing pancreatobiliary cancer (PBca). The aim of this study was to identify serum microRNA (miRNA) signatures comprising reproducible and disease-related miRNAs.MethodsThis multicenter study involved patients with treatment-naïve PBca and healthy participants. The optimized serum processing conditions were evaluated using t-distributed stochastic neighbor embedding (t-SNE) visualization. Serum miRNA candidates for disease association were selected using weighted gene coexpression network analysis (WGCNA). A miRNA signature combining multiple serum miRNAs was tested in exploratory, validation, and independent validation sets. The synthesis and secretion of diagnostic miRNAs were evaluated using human pancreatic cancer cells.ResultsIn total, 284 (150 healthy and 134 PBca) of 827 serum samples were processed within 2 h of blood collection before freezing, distributed in the same area as that in the t-SNE map, and assigned to an exploratory set. The 193 optimized samples were assigned to either the validation (50 healthy, 47 PBca) or independent validation (50 healthy, 46 PBca) set. Index-1, a combination of five serum miRNAs (hsa-miR-1343-5p, hsa-miR-4632-5p, hsa-miR-4665-5p, hsa-miR-665, and hsa-miR-6803-5p) with disease association in WGCNA, showed a sensitivity and specificity of > 80% and an AUC outperforming that of CA19-9 in the exploratory, validation, and independent validation sets. The AUC of Index-1 was superior to that of CA19-9 (0.856 vs. 0.649, p = 0.038) for detecting T1 tumors. miR-665, a component of Index-1, was expressed in human pancreatic cancer cells, and its transfection inhibited cell growth.ConclusionsThe serum miRNA signature Index-1 is useful for detecting PBca and could facilitate the early diagnosis of PBca. These findings can help improve clinical PBca detection by providing an optimized biomarker that overcomes the limitations of the current standard.

Management of Clinically Node-Negative Salivary Gland Cancer: Observation, Neck Dissection, or Neck Irradiation?

Salivary gland malignancies are heterogeneous tumors with highly variable outcomes. Elective neck management options include observation, neck dissection (ND), and neck irradiation (NI). We sought to compare outcomes of cN0 salivary gland cancer by elective neck management. An IRB-approved registry was queried for cN0 salivary gland cancers and categorized based on neck management into observation, ND, NI, and ND + NI groups. cN0 included no evidence of clinical or radiographic metastatic lymphadenopathy. A total of 445 patients were included with 203 in observation, 83 ND, 71 NI, and 88 ND + NI. Median follow-up was 60.8 months (range 0.4-258). There were 47% clinical T1 tumors, 29% T2, and 12% of each T3 and T4. Exactly 90% were cN0 and 10% with borderline lymph node(s). The major salivary gland was the most common site (74%) and the most common histologies included 28% mucoepidermoid and 20% adenoid cystic. Risk factors associated with regional recurrence include age, borderline lymph node features, pathologic T and N stage, poorly differentiated, positive margin, lymphovascular space invasion, and extranodal extension (all p < 0.05). There was no significant difference in local (9.9%-16.7%, p = 0.6) or regional (3.9%-9.4%, p = 0.76) recurrence between all four groups. Five-year distant recurrence was significantly different at 7% for observation, 16% in ND, 25% in NI, and 37% in ND + NI (p < 0.001). Ten-year OS estimates were 78% for observation, 66% for ND, 69% for NI, and 52% in ND + NI (p < 0.001). For patients with cN0 salivary gland cancer, ND and NI yield similar regional control in appropriately selected patients. In high-risk patients with several adverse risk features ND + NI results in favorable regional control but distant metastasis is a driving factor affecting overall survival.

Canine lung carcinoma-A descriptive review.

Primary lung cancer is a relatively uncommon tumor in dogs, accounting for about 1% of all canine malignancies. Clinical signs in affected dogs can range from being asymptomatic to exhibiting chronic cough, and in rare cases, dyspnoea. Surgical excision of the primary tumor, along with resection of the affected locoregional lymph nodes is the preferred treatment option for most cases. Although chemotherapy, targeted therapy and radiation therapy have been employed, their effectiveness remain controversial. Dogs with stage T1 tumors can experience extended survival times of up to 2 years. However, the prognosis for dogs with advanced metastatic tumors is generally very poor. This review article discusses the etiology, clinical signs, diagnosis, staging, treatment options, and prognosis of primary lung carcinoma in dogs.

Neoadjuvant Chemotherapy for T3 Tumors in the Era of Precision Medicine-Biology Is Still King.

Clinical T3 (cT3) breast cancer (BC) presents a challenge for achieving cosmetically acceptable breast conservation, and neoadjuvant chemotherapy (NAC) is commonly used for cytoreduction in these high-risk cancers. MammaPrint® risk-of-recurrence and BluePrint® molecular subtyping genomic signatures have demonstrated high accuracy in predicting chemotherapy benefits. Here, we examined the utility of MammaPrint/BluePrint for predicting pathological Complete Response (pCR) rates to NAC among 404 patients diagnosed with cT3 early-stage BC. The association of genomic subtype and clinical features with the likelihood of pCR was evaluated by multivariate logistic regression. Differences in pCR rates between genomic risk categories were evaluated by a two-sided proportional z-test and stratified by nodal status. MammaPrint/BluePrint subtyping was associated with significantly higher odds ratios (ORs) for pCR in MammaPrint High-Risk/BluePrint Basal-Type (OR = 3.06, 95% CI: 1.15-8.19, p = 0.025) and HER2-Type (OR = 6.27, 95% CI: 2.19-19.38, p = 0.001) compared to BluePrint Luminal-Type. Of the 209 patients with hormone receptor-positive, HER2-negative disease, 6.7% achieved pCR, and MammaPrint High-Risk was associated with a significantly higher pCR rate (9.3%) compared to MammaPrint Low-Risk cancers (0%), regardless of nodal involvement (p = 0.036). These data show that for patients with MammaPrint Low-Risk, cT3 tumors are less likely to have clinically impactful cytoreduction from NAC, regardless of nodal involvement.

Phase 2 pilot trial of tislelizumab plus low-dose nab-paclitaxel for extensive very high-risk non-muscle-invasive bladder cancer.

Combinations of immune checkpoint inhibitors and nab-paclitaxel have improved outcomes in advanced urothelial carcinoma and muscle-invasive bladder cancer. This study evaluates the safety and efficacy of tislelizumab combined with low-dose nab-paclitaxel in extensive very high-risk (VHR) non-muscle-invasive bladder cancer (NMIBC). TRUCE-02 was a single-arm phase 2 trial that included 63 patients with visually incomplete resection and/or high-volume high-grade T1 tumors (with or without carcinoma in situ), who were ineligible for or declined radical cystectomy. Patients received intravenous tislelizumab (200 mg on day 1) and nab-paclitaxel (200 mg on day 2) every 3 weeks, with assessment approximately 3 months after initial administration. The primary endpoint was the complete response rate of high-risk disease. Main secondary endpoints included safety and duration of complete response. The safety analysis included all 63 patients and the efficacy analysis included 59 patients. Thirty-seven patients [62.7%; 95% confidence interval (CI), 49.1-75.0%] achieved a complete response of high-risk disease, with a 24-month sustained response rate of 96.3% (95% CI, 89.4-100.0%). Grade 3-4 treatment-related adverse events occurred in nine patients (14%), with no fatal events reported. Tislelizumab plus low-dose nab-paclitaxel was well-tolerated and showed promising antitumor activity, making it a potential alternative for extensive VHR NMIBC patients who are ineligible for or decline radical cystectomy.

Local resection in rectal cancer: When, who and how?

Local resection (LR) in rectal cancer is indicated in stage T1N0M0 without unfavorable pathological factors, achieving oncologically satisfactory outcomes through transanal endoscopic surgery techniques. However, the initial step involves accurate staging and selection of these tumors through specific tests conducted in specialized colorectal units. For T2N0M0 tumors and T1 tumors with poor prognostic factors, the standard treatment is total mesorectal excision (TME), a procedure associated with high postoperative morbidity and mortality, functional impairments, and reduced quality of life. Therefore, new organ-preservation strategies are being explored as alternatives to TME. These include neoadjuvant therapy combined with LR, which has shown promising results, and neoadjuvant therapy followed by a "Watch and Wait" approach -where patients with complete clinical response are selected for strict surveillance- as an ideal future treatment, although there are still current challenges to be addressed.

Immediate second resection versus restage transurethral resection of bladder tumor: A prospective randomized clinical trial (IMMERSE trial).

The role of repeat transurethral resection of bladder tumor (TURBT) for the management of nonmuscle invasive bladder carcinoma is debated, especially when initial resections include detrusor muscle. This study compares immediate second resection (additional deep biopsies in the same session) with standard restage TURBT performed 2-6 weeks post-initial TURBT to determine adequacy in detrusor muscle sampling and compare the disease rate at restage TURBT in both groups. A randomized trial was conducted at a tertiary care hospital, including patients aged ≥18 years undergoing TURBT with complete primary tumor resection. Cases were randomized into two groups i.e., 'standard TURBT' (complete tumor resection with a deep biopsy) and "immediate second resection" (complete tumor resection, deep biopsy and additional deep biopsies). The primary endpoint was the presence of detrusor muscle in biopsy specimens, analyzed by a single pathologist. Secondary endpoints included perioperative complications, residual/ recurrent tumors, and factors affecting these recurrences. The study included 83 patients: 44 in the 'standard TURBT' group and 39 in the 'immediate second resection' group. The detrusor muscle was present in 66% of standard TURBT cases and 97% of immediate second resection cases, showing a statistically significant improvement (P = 0.000). Residual disease was found in 41% of restage TURBT patients in the standard group and 15% in the immediate second resection group, the majority being high-grade and T1 tumors (P = 0.028). There were no significant differences in tumor grade or perioperative complications between the groups. However, immediate second resection showed 18% higher detrusor muscle sampling rates than standard re-stage TURBT done at 2-6 weeks (P = 0.021). Immediate second resection at the time of initial TURBT significantly improves detrusor muscle sampling rates and decreases residual tumors at restage. Despite higher muscle sampling, a considerable proportion of patients still exhibited residual or recurrent tumors in both groups, emphasizing the need for improved detection and biopsy techniques during primary TURBT.

Quantitative magnetic resonance imaging responses in head and neck cancer patients treated with magnetic resonance-guided hypofractionated radiation therapy.

Quantitative MRI (qMRI) has been explored for detecting tumor changes during radiation therapy (RT) in head and neck squamous cell cancer (HNSCC). Clinical trials show prolonged survival with PD-1 targeted immune checkpoint inhibition. Hypofractionated radiation regimens are being studied to counteract radioresistant clonogen formation. This study aims to use daily qMRI monitoring in these therapies. The objective of this exploratory study was to investigate if qMRI can detect tumor microenvironment changes during hypofractionated RT in a phase I trial of Dose-Escalated Hypofractionated Adaptive Radiotherapy (DEHART). Seventeen subjects with advanced HNSCC underwent MR-guided RT with daily qMRI using a 15-fraction regimen to a cumulative dose of 50, 55, or 60Gy. A 1.5T MRI-Linac collected daily intravoxel incoherent motion (IVIM), T1, and T2 mappings. Median primary tumor ADC, D, D*, f, T1, and T2 were calculated, using paraspinal muscle as a control. qMRI parameters were analyzed by treatment condition and length using linear mixed effect models and nonparametric tests. Significant (p<0.05) increases in ADC, D, f, and T2 were observed over treatment duration for multiple conditions. Daily monitoring enhanced result significance compared to weekly collection. Daily qMRI effectively monitors tumor response over short periods and varying treatment conditions. Further studies on radiation and systemic therapy combinations in HNSCC could benefit from daily qMRI data collection.

Achieving Textbook Outcomes with Robotic Assisted Ivor Lewis Esophagectomy: A Single Center Experience with 150 Consecutive Patients.

With published randomized data, minimally invasive esophagectomy (MIE) is becoming more popular, however a sizable variability in techniques and outcomes still exist. This is a retrospective analysis of 150 consecutive robotic assisted minimally invasive esophagectomies (RAMIE) from a prospectively maintained database from 2020-2024, at a single comprehensive cancer center. We aim to evaluate the textbook outcome rate after RAMIE. 150 consecutive patients underwent RAMIE from 2020 -2024. Tumor location included esophagus in 18, type 1 GE junction in 52, type 2 in 71, and type 3 in 9 patients. Majority of patients had clinical stage T3 tumors. Neoadjuvant therapy was utilized in 85%. Complete pathologic response was seen in 27%. Median number of lymph nodes retrieved were 21. Anastomotic leak occurred in 2 patients, none requiring a reoperation. Median hospital stay was 7 days. Thirty day and 90-day mortality were 0.7% and 1.3% respectively. 90-day stricture with endoscopic dilation was also 0.7%. 90% patients had a textbook outcome. This single center experience highlights that a combination of robotic platform and a side-to-side stapled anastomotic technique helps achieve exceptional postoperative outcomes for MIE with a textbook outcome rate of 90%. With increasing worldwide adoption of MIE, this seems to be an appropriate time to standardize operative technique to optimize postoperative outcomes.

Impact of the tumor microenvironment on delivery of nanomedicine in tumors treated with ultrasound and microbubbles.

The delivery of nanoparticles to tumors has been shown preclinically to be improved by microbubble-mediated ultrasound. However, the mechanisms and biological effects not fully understood. In this study, we explored the influence of the tumor microenvironment on nanoparticle uptake and microdistribution both with and without ultrasound and microbubble treatment. Three murine tumor models, KPC (pancreatic ductal adenocarcinoma), 4 T1 (triple negative mammary carcinoma) and CT26 (colon carcinoma), were characterized with respect to extracellular matrix composition, tumor stiffness and perfusion. KPC and 4 T1 tumors presented higher levels of collagen and hyaluronic acid and were stiffer compared to CT26, whereas all three tumors had similar levels of sulfated glycosaminoglycans. Furthermore, the 4 T1 tumors appeared poorly vascularized with a lower cell density compared to KPC and CT26. All three tumors presented similar nanoparticle uptake, but extravasated nanoparticles traveled significantly shorter in KPC tumors compared to 4 T1 and CT26. The effect of ultrasound and microbubble treatment on the tumor uptake and penetration of polymer nanoparticles into the extracellular matrix were evaluated using a treatment protocol previously shown to increase nanoparticle delivery to tumors. Interestingly, we found a significant increase in nanoparticle uptake in the soft CT26 tumor, but no effect of the ultrasound treatment in the stiff KPC and 4 T1 tumors, suggesting that tumor stiffness is an important parameter for treatment with ultrasound and microbubbles. Ultrasound treatment resulted in a modest but not statistically significant improvement in nanoparticle penetration through the extracellular matrix. In tumors demonstrating increased uptake of nanoparticles following ultrasound treatment, the uptake correlated positively with blood volume. These findings emphasize the importance of taking the tumor microenvironment into consideration when optimizing ultrasound parameters for delivery of nanomedicine.

Cascade-Activatable Nanoprodrug System Augments Sonochemotherapy of Bladder Cancer.

Sonochemotherapy (SCT) has emerged as a powerful modality for cancer treatment by triggering excessive production of reactive oxygen species (ROS) and controlled release of chemotherapeutic agents under ultrasound. However, achieving spatiotemporally controlled release of chemotherapeutic agents during ROS generation is still an enormous challenge. In this work, we developed a cascade-activated nanoprodrug (CAN) system that utilizes a reversible covalent Schiff base mixed with a hypoxia-activatable camptothecin (CPT) prodrug. Briefly, the designed fluorinated CAN system is self-assembled into nanoparticles under aqueous conditions, which could penetrate deep tumors to offer sufficient oxygen for ultrasound-triggered ROS production. Consequently, the nanoparticles substantially exacerbated the hypoxia of the tumor microenvironment (TME) by elevating oxygen consumption. The aggravated hypoxia in turn served as a positive amplifier to boost the tumor-specific CPT release of Azo-CPT prodrug, which made up for the insufficient treatment efficacy of sonodynamic therapy (SDT). On this basis, we observed a substantial reduction, approximately 3.5-fold, in the half-maximal inhibitory concentration (IC50) of the CAN system compared to that of free CPT in bladder cancer cell lines (T24). Furthermore, the CAN system demonstrated potent antitumor efficacy with reduced side effects, resulting in regression and eradication of T24 tumors in various mouse models. In summary, the CAN system can be easily extended by incorporating different chemotherapeutic agents, showing great potential to revolutionize the clinical management paradigm of bladder cancer.

Axillary Surgery in Breast Cancer - Primary Results of the INSEMA Trial.

Whether surgical axillary staging as part of breast-conserving therapy can be omitted without compromising survival has remained unclear. In this prospective, randomized, noninferiority trial, we investigated the omission of axillary surgery as compared with sentinel-lymph-node biopsy in patients with clinically node-negative invasive breast cancer staged as T1 or T2 (tumor size, ≤5 cm) who were scheduled to undergo breast-conserving surgery. We report here the per-protocol analysis of invasive disease-free survival (the primary efficacy outcome). To show the noninferiority of the omission of axillary surgery, the 5-year invasive disease-free survival rate had to be at least 85%, and the upper limit of the confidence interval for the hazard ratio for invasive disease or death had to be below 1.271. A total of 5502 eligible patients (90% with clinical T1 cancer and 79% with pathological T1 cancer) underwent randomization in a 1:4 ratio. The per-protocol population included 4858 patients; 962 were assigned to undergo treatment without axillary surgery (the surgery-omission group), and 3896 to undergo sentinel-lymph-node biopsy (the surgery group). The median follow-up was 73.6 months. The estimated 5-year invasive disease-free survival rate was 91.9% (95% confidence interval [CI], 89.9 to 93.5) among patients in the surgery-omission group and 91.7% (95% CI, 90.8 to 92.6) among patients in the surgery group, with a hazard ratio of 0.91 (95% CI, 0.73 to 1.14), which was below the prespecified noninferiority margin. The analysis of the first primary-outcome events (occurrence or recurrence of invasive disease or death from any cause), which occurred in a total of 525 patients (10.8%), showed apparent differences between the surgery-omission group and the surgery group in the incidence of axillary recurrence (1.0% vs. 0.3%) and death (1.4% vs. 2.4%). The safety analysis indicates that patients in the surgery-omission group had a lower incidence of lymphedema, greater arm mobility, and less pain with movement of the arm or shoulder than patients who underwent sentinel-lymph-node biopsy. In this trial involving patients with clinically node-negative, T1 or T2 invasive breast cancer (90% with clinical T1 cancer and 79% with pathological T1 cancer), omission of surgical axillary staging was noninferior to sentinel-lymph-node biopsy after a median follow-up of 6 years. (Funded by the German Cancer Aid; INSEMA ClinicalTrials.gov number, NCT02466737.).

The Clinical Characteristics of a Stage II Colorectal Cancer T4 Tumor: A Ten-Year Single-Center Research Report.

The tumor staging of colorectal cancer (CRC) plays a significant role in both treatment and prognosis, impacting surgical planning and adjuvant therapy decisions. Currently, the staging of CRC is based on the TNM system developed by the American Joint Committee on Cancer. Prior studies have suggested that survival rates and recurrent rates of T4a tumors appear to be worse than that of T4b tumors, although there is currently no consensus. Therefore, we collected patient data from Taichung Veterans General Hospital over the past decade in order to conduct further research. Between 2010 and 2018, a total of 5760 newly diagnosed CRC patients were seen at the hospital. To eliminate the influence of any local lymph node involvement or distant organ metastasis on the research results, we focused on patients with pathologic Stage IIc disease (T4a-bN0M0). Patients with rectal cancer who had received neoadjuvant concurrent chemoradiotherapy were excluded. Ultimately, 132 patients were included in this study. A multivariate Cox regression analysis was conducted to identify independent risk factors for both 10-year cancer-specific survival (CSS) and overall survival (OS). A total of 132 patients were included in the study, with 90 classified as T4a and 42 as T4b. The 10-year CSS for pT4a and pT4b was 72.5% and 56.5%, respectively, with a p-value of 0.011. The 10-year OS for pT4a and pT4b was 48.4% and 42.5%, respectively, with a p-value of 0.086. There was no significant difference in the site of first recurrence between the pT4a and pT4b groups (p-value = 0.936). Overall, patients who received adjuvant chemotherapy therapy had a significantly better prognosis (p-value < 0.05). However, there was no significant difference in prognosis between oral 5-FU and FOLFOX. Based on our data, patients diagnosed with pathologic T4aN0M0 CRC appeared to experience a trend toward better 10-year OS when compared to those with T4bN0M0 disease, but this trend lacks statistical significance. Patients with locally advanced Stage II colon cancer clearly benefited from adjuvant chemotherapy therapy; therefore, FOLFOX may not necessarily be required.