Tumor Border Research Articles

Multivariate analysis of breast tissue using optical parameters extracted from a combined time-resolved fluorescence and diffuse reflectance system for tumor margin detection.

Breast conservation therapy is the preferred technique for treating primary breast cancers. However, breast tumor margins are hard to determine as tumor borders are often ill-defined. As such, there exists a need for a clinically compatible tumor margin detection system. A combined time-resolved fluorescence and diffuse reflectance (TRF-DR) system has been developed to determine the optical properties of breast tissue. This study aims to improve tissue classification to aid in surgical decision making. Normal and tumor breast tissue were collected from 80 patients with invasive ductal carcinoma and measured in the optical system. Optical parameters were extracted, and the tissue underwent histopathological examination. In total, 761 adipose, 77 fibroglandular, and 347 tumor spectra were analyzed. Principal component analysis and decision tree modeling were performed using only TRF optical parameters, only DR optical parameters, and using the combined datasets. The classification modeling using TRF data alone resulted in a tumor margin detection sensitivity of 72.3% and specificity of 88.3%. Prediction modeling using DR data alone resulted in greater sensitivity and specificity of 80.4% and 94.0%, respectively. Combining both datasets resulted in the improved sensitivity and specificity of 85.6% and 95.3%, respectively. While both sensitivity and specificity improved with the combined modeling, further study of fibroglandular tissue could result in improved classification. The combined TRF-DR system showed greater tissue classification capability than either technique alone. Further work studying more fibroglandular tissue and tissue of mixed composition would develop this system for intraoperative use for tumor margin detection.

Prognostic significance of collagen signatures at breast tumor boundary obtained by combining multiphoton imaging and imaging analysis.

Collagen features in breast tumor microenvironment is closely associated with the prognosis of patients. We aim to explore the prognostic significance of collagen features at breast tumor border by combining multiphoton imaging and imaging analysis. We used multiphoton microscopy (MPM) to label-freely image human breast tumor samples and then constructed an automatic classification model based on deep learning to identify collagen signatures from multiphoton images. We recognized three kinds of collagen signatures at tumor boundary (CSTB I-III) in a small-scale, and furthermore obtained a CSTB score for each patient based on the combined CSTB I-III by using the ridge regression analysis. The prognostic performance of CSTB score is assessed by the area under the receiver operating characteristic curve (AUC), Cox proportional hazard regression analysis, as well as Kaplan-Meier survival analysis. As an independent prognostic factor, statistical results reveal that the prognostic performance of CSTB score is better than that of the clinical model combining three independent prognostic indicators, molecular subtype, tumor size, and lymph nodal metastasis (AUC, Training dataset: 0.773 vs. 0.749; External validation: 0.753 vs. 0.724; HR, Training dataset: 4.18 vs. 3.92; External validation: 4.98 vs. 4.16), and as an auxiliary indicator, it can greatly improve the accuracy of prognostic prediction. And furthermore, a nomogram combining the CSTB score with the clinical model is established for prognosis prediction and clinical decision making. This standardized and automated imaging prognosticator may convince pathologists to adopt it as a prognostic factor, thereby customizing more effective treatment plans for patients.

Predictive value of MRI-detected tumor deposits in locally advanced rectal cancer.

Although tumor deposits (TDs) are not the same as lymph nodes, the prognosis of patients with TDs is similar or worse than that of patients with metastatic lymph nodes. TDs are mostly assessed by the histology of samples after surgery, thus, not helpful for preoperative treatment strategies. The primary objective of this study was to detect TDs by MRI and evaluate its predictive value. A total of 114 patients with rectal cancer were retrospectively analyzed. Clinicopathological and MRI data mainly including MRI- detected TDs (mTDs), tumor border configuration (TBC) on MRI, MRI-detected extramural vascular invasion (mEMVI), MRI-detected lymph node metastasis (mLN), MRI T stage, MRI N stage, the range of rectal wall involved by the tumor, peritoneal reflection invasion, tumor length, tumor location, cord sign at the tumor edge, nodular protrusion at the tumor edge, maximal extramural depth and pathology-proven lymph node involvement (pLN) were evaluated. The correlation of MRI factors with postoperative distant metastasis (PDM) and pLN were analyzed by univariate analysis and multivariate logistic regression analysis, and nomograms were established based on the latter. The diagnostic efficiency was evaluated by the receiver operating characteristic curve (ROC) and area under the curve (AUC). A total of 38 cases of pLN, 13 of PDM and 17 of pathology-proven TDs (pTDs) were found. Ten cases of PDM and 22 cases of pLN in 30 mTDs cases were also found. Chi-square test showed that mTDs, mLN, TBC, mEMVI, MRI T stage, nodular protrusion, cord sign, maximal extramural depth and peritoneal reflection invasion were correlated with PDM and pLN (P<0.05). mTDs and peritoneal reflection invasion were independent risk factors for PDM (odds ratio: 10.15 and 8.77, P<0.05), mTDs and mLN were independent risk factors for pLN (odds ratio: 5.50 and 5.91, P<0.05), and Hosmer-Lemeshow test showed that the results of two models were not statistically significant, suggesting that the fit was good. On this basis, two nomograms for predicting PDM and pLN were confirmed by Bootstrap self-sampling, and the C-indices of the two nomograms were 0.837 and 0.817, respectively. The calibration curves and ROC curves of the two nomograms showed that the correlation between the predicted and the actual incidence of PDM and pLN was good. The DeLong test showed that the predictive efficiency of the nomogram in predicting pLN was better than that of mLN (P=0.0129). mTDs are a risk factor for PDM and lymph node metastasis. The two nomograms based on mTDs showed a good performance in predicting PDM and lymph node metastasis, possessing a certain clinical value.

Abstract B030: Form and function in intratumoral immune organization: Understanding the cellular composition of TCF1+ CD8+ T cell niches in human cancer

Abstract Tumor infiltrating T cells are a positive prognosticator in many tumor types, and our prior work demonstrated that in renal cell carcinoma, patients with higher CD8 T cell infiltration have improved survival (Jansen Nature 2019). We described that this T cell response is supported by TCF1+ stem-like CD8 T cells, which reside within dense regions of closely clustered antigen presenting cells within the tumor. Interestingly, aggregations of immune cells have also been described in other settings and termed ‘tertiary lymphoid structures’ (TLS), raising an important question of whether the described immune niches are similar to these TLS or if they represent a distinct type of peripheral immune organization. In the work presented here, we use quantitative immunofluorescence image analysis to examine the cellular composition and organization of intratumoral immune niches, TLS, and secondary lymphoid tissue. The novel data presented here describes how immune niches are distinct from TLS and are more similar to the organization of T cell zones in secondary lymphoid tissue. Immune niches are T cell dominant structures, with T cell and antigen presenting cell compartments similar to T cell zones, whereas these niches profoundly lack the B cell presence seen in TLS and B cell zones of secondary lymphoid tissue. Immune niches are comparatively small in size (50-200um), while TLS are much larger (often &amp;gt;1mm), and, importantly, immune niches are found inside the tumor border, while TLS are located peripherally in tumor tissue. Notably, we find that immune niches have a marked presence of aSMA+ stromal cells, which are similar to those found in T cell zones but absent in B cell zones and TLS. When probed by flow cytometry and RNAseq, we find that aSMA+ stroma in immune niches are myofibroblast-like, similar those known to maintain the structure of secondary lymphoid tissues, and are distinct from those found in healthy kidney tissue. These data suggest these aSMA+ cells may play an important role in the organization of immune niches in tumor tissue. As we have shown that a robust T cell response is beneficial for patient outcomes, it is crucial to understand the mechanisms which support that response. Recently, our group defined that CD8 T cell activation in cancer is comprised of two phases, with an initial priming phase in the lymph node and a second phase of effector program acquisition in the tumor tissue (Prokhnevska Immunity 2023). We suggest that these immune niches represent an important hub for this development of T cell function, which is required for the robust, effective anti-tumor T cell response that supports improved patient outcomes and is the basis for the response to immunotherapy. Advancing our understanding of intratumoral immune organization will allow for enhanced biomarker discovery, improvement in existing therapies, and innovation in developing novel therapeutic strategies that will convert immunologically “cold” tumors to be immunologically “hot” and enhance anti-tumor immunity. Citation Format: Caroline S. Jansen, BaoHan Vo, Ewelina Sobierajska, Rachel Greenwald, Patrick Mullane, Nataliya Prokhnevska, Maria Cardenas, Mehmet Asim Bilen, Adeboye O. Osunkoya, Viraj A. Master, Haydn T. Kissick. Form and function in intratumoral immune organization: Understanding the cellular composition of TCF1+ CD8+ T cell niches in human cancer [abstract]. In: Proceedings of the AACR Special Conference: Advances in Kidney Cancer Research; 2023 Jun 24-27; Austin, Texas. Philadelphia (PA): AACR; Cancer Res 2023;83(16 Suppl):Abstract nr B030.

Evaluation of correspondence between clinical and pathological margins in oral squamous cell carcinoma

Background: Microscopically, oral Squamous Cell Carcinoma (SCC) spreads more than the gross tumor. Thus it is recommended to resect the tumor with a proper safe margin. The aim of this study was to evaluate the correspondence between clinical and histopathological margins in oral SCC.&#x0D; Methods: Samples were collected from patients diagnosed as oral SCC and referred to Iran Cancer Institute on 2015. All margins of tumors were determined by a marker and then the tumors were resected with 1cm safe margin. The superior, inferior, left and right borders were marked and examined microscopically. The lowest distance between tumor cells and border of resected tissue was considered as pathological margin. The cases with pathological margin less or more than 5 millimeters were classified as close and free margin group, respectively.&#x0D; Results: forty-four specimens (20 females and 24 males), definitely diagnosed as SCC, were examined. The mean age was 61 years old. 19 cases (43.2%) were in the mandible; 23 cases (52.3%) in the tongue and 2 cases (4.5%) in the maxilla. 16 cases (38.4%) were free margin and 28 cases (63.6%) were close margin and the mean pathological margin was 3.52mm.&#x0D; Conclusion: for some cases, especially SCCs of the mandible, 1-centimeter margin is not adequate to achieve free margins, thus evaluating tumor location, size and stage for more resection seems worthwhile and advisable and can decrease the risk of relapse after resection.

Proposal of a grading system for squamous cell carcinoma of the lung - the prognostic importance of tumour budding, single cell invasion, and nuclear diameter.

The prognostic markers of lung squamous cell carcinoma (LSCC) are less investigated. The aim of our study was to evaluate tumour budding (TB), minimal cell nest size, nuclear diameter (ND), and spread through air spaces (STAS) among patients with resected LSCC, semi-quantitatively. Furthermore, we aimed to identify a grading system for the best prognostic stratification of LSCC. Patients who underwent surgical resection at the Department of Surgery, University of Szeged between 2010 and 2016 were included. Follow-up data were collected from medical charts. Morphological characteristics were recorded from histologic revision of slides. Kaplan-Meier analysis, log rank test and Cox proportional-hazards model, ROC curve analysis, and intraclass correlation were utilised. Altogether 220 patients were included. In univariate analysis, higher degree of TB, infiltrative tumour border, larger ND, the presence of single cell invasion (SCI) and STAS were associated with adverse prognosis. Based on our results, we proposed an easily applicable grading scheme focusing on TB, ND, and SCI. In multivariate analysis, the proposed grading system (pOS< 0.001, pRFS< 0.001) and STAS (pOS= 0.008, pRFS< 0.001) were independent prognosticators. Compared to the previously introduced grading systems, ROC curve analysis revealed that the proposed grade had the highest AUC values (AUCOS: 0.83, AUCRFS: 0.78). Each category of the proposed grading system has good (ICC: 0.79-0.88) reproducibility. We validated the prognostic impact of TB, SCI, ND, and STAS in LSCC. We recommend a reproducible grading system combining TB, SCI, and ND for proper prognostic stratification of LSCC patients. Further research is required for validation of this grading scheme.

Construction and Application of a Nomogram for Predicting Benign and Malignant Parotid Tumors.

A prediction model of benign and malignant differentiation was established by magnetic resonance signs of parotid gland tumors to provide an important basis for the preoperative diagnosis and treatment of parotid gland tumor patients. The data from 138 patients (modeling group) who were diagnosed based on a pathologic evaluation in the Department of Stomatology of Jilin University from June 2019 to August 2021 were retrospectively analyzed. The independent factors influencing benign and malignant differentiation of parotid tumors were selected by logistic regression analysis, and a mathematical prediction model for benign and malignant tumors was established. The data from 35 patients (validation group) who were diagnosed based on pathologic evaluation from September 2021 to February 2022 were collected for verification. Univariate and multivariate logistic regression analysis showed that tumor morphology, tumor boundary, tumor signal, and tumor apparent diffusion coefficient (ADC) were independent risk factors for predicting benign and malignant parotid gland tumors ( P < 0.05). Based on multivariate logistic regression analysis of the modeling group, a mathematical prediction model was established as follows: Y = the ex/(1 + ex) and X = 0.385 + (1.416 × tumor morphology) + (1.473 × tumor border) + (1.306 × tumor signal) + (2.312 × tumor ADC value). The results showed that the area under the receiver operating characteristic curve of the model was 0.832 (95% confidence interval, 0.75-0.91), the sensitivity was 82.6%, and the specificity was 70.65%. The validity of the model was verified using validation group data, for which the sensitivity was 85.71%, the specificity was 96.4%, and the correct rate was 94.3%. The results showed that the area under receiver operating characteristic curve was 0.936 (95% confidence interval, 0.83-0.98). Combined with tumor morphology, tumor ADC, tumor boundary, and tumor signal, the established prediction model provides an important reference for preoperative diagnosis of benign and malignant parotid gland tumors.

Tumor Control Probability and Small-Scale Monte Carlo Dosimetry: Effects of Heterogenous Intratumoral Activity Distribution in Radiopharmaceutical Therapy.

In radiopharmaceutical therapy, intratumoral uptake of radioactivity usually leads to heterogeneous absorbed dose distribution. The likelihood of treatment success can be estimated with the tumor control probability (TCP), which requires accurate dosimetry, estimating the absorbed dose rate per unit activity to individual tumor cells. Methods: Xenograft cryosections of the prostate cancer cell line LNCaP treated with [177Lu]Lu-PSMA-617 were evaluated with digital autoradiography and stained with hematoxylin and eosin. The digital autoradiography images were used to define the source in a Monte Carlo simulation of the absorbed dose, and the stained sections were used to detect the position of cell nuclei to relate the intratumoral absorbed dose heterogeneity to the cell density. Simulations were performed for 225Ac, 177Lu, and 90Y. TCP was calculated to estimate the mean necessary injected activity for a high TCP. A hypothetical case of activity mainly taken up on the tumor borders was generated and used to simulate the absorbed dose. Results: The absorbed dose per decay to tumor cells was calculated from the staining and simulation results to avoid underestimating the tumor response from low absorbed doses in tumor regions with low cell density. The mean of necessary injected activity to reach a 90% TCP for 225Ac, 177Lu, and 90Y was found to be 18.3 kBq (range, 18-22 kBq), 24.3 MBq (range, 20-29 MBq), and 5.6 MBq (range, 5-6 MBq), respectively. Conclusion: To account for the heterogeneous absorbed dose generated from nonuniform intratumoral activity uptake, dosimetry models can estimate the mean necessary activity to reach a sufficient TCP for treatment response. This approach is necessary to accurately evaluate the efficacy of suggested radiopharmaceuticals for therapy.

Differential Impact of Spread Through Air Spaces on Subtypes of Early-stage Lung Cancer.

To investigate the prognostic significance of STAS (Spread through air spaces) and its effect on survival in the various types of non-small cell lung cancer (NSCLC). Descriptive analytical study. Place and Duration of the Study: Kartal Dr. Lutfi Kirdar City Hospital, Istanbul, Turkiye,between 2018 and 2021. Early-stage lung cancer patients who underwent lobectomy were included. STAS was defined as presence of tumour cell clumps, solid nests or set of single cells located in airway spaces apart from the main tumour border and determined by pathological work-up. The clinical significance of STAS was investigated by means of histopathological subtype, tumour size, and maximum standardised uptake value (SUVmax) on PET-CT scan in early-stage lung cancer by grouping it as adenocarcinoma and non-adenocarcinoma. Five-year overall and disease-free survival, and recurrence were the outcome measures. A total of 165 patients were included in the study. No recurrence was observed in 125 patients, 40 patients developed recurrence. Five-year overall survival (OS) was 69.6% in STAS (+) cohort and 74.5% in STAS (-) cohort (p=0.88). Five-year disease-free survival (DFS) was 51.1% in STAS (+) cohort and 73.1% for STAS (-) cohort (p=0.034). While the absence of STAS in the adenocarcinoma group was associated with better DFS, lower SUVMax and smaller tumour size, similar results were not found to be at statistically significant level in the non-adenocarcinoma group. STAS positivity makes a difference in DFS, tumour size and SUVmax, especially in adenocarcinoma, however, it does not create a significant difference in survival or clinic pathological features in the non-adenocarcinoma. Lung Cancer, Lobectomy, Spread through air spaces, Survival, Prognosis.

Single-cell analysis reveals HBV-specific PD-1+CD8+ TRM cells in tumor borders are associated with HBV-related hepatic damage and fibrosis in HCC patients

Immune checkpoint blockade (ICB) treatment of hepatocellular carcinoma (HCC) patients with hepatitis B virus (HBV) infection may activate viral-specific T cells to attack HBV infected hepatocytes and thus induce immune-related liver injury. Therefore, it is important to deeply understand the impacts of HBV infection on HCC immune microenvironment in order to better design effective immunotherapies for HBV+ (HBV infected) HCC patients. Here, We performed cytometry by time-of-flight (CyTOF) analyses to characterize the distinct immune compositions of HCC tumors, tumor borders, and their associations with HCC/HBV related clinical characteristics. We identified 31 distinct immune clusters and found significant associations between immune signatures with clinicopathological features of HCC. We further revealed the HBV infection had more effects on shaping immune compositions in tumor borders than in tumors, with the significant enrichment of HBV-specific PD-1+CD8+ tissue-resident memory T (TRM) cells in tumor borders of HBV+ patients. We confirmed this subset with a more exhausted phenotype and respond more actively under anti-PD-L1 treatment, suggesting its involvement in immune-related liver injury induced by ICB treatment to HBV+ HCC patients. Our study shows it may be necessary to consider antiviral prophylaxis for HBV+ HCC patients receiving ICB treatment.

Distance between tumor and bronchial resection margin is an independent predictor of recurrence-free survival and overall survival in primary endobronchial neoplasm.

The distance between tumor and bronchial resection margin (DBTM) had no clear standard in lung cancer surgery. We aimed to select the optimal cut-off value to provide a standard for surgery of the patients with primary endobronchial neoplasm. We retrospectively analyzed patients with primary endobronchial neoplasm who underwent surgical resection between 2005 and 2012. The receiver operating characteristic curves and the Youden index were used to calculate the optimal cut-off value of the DBTM. Propensity score matching was applied to reduce selection bias. Survival was assessed with Kaplan-Meier analysis, log-rank test and Cox proportional hazards model. A total of 1048 patients comprised in the study cohort and 1.7cm was determined the optimal cut-off value, including 531 grouped in DBTM ≤ 1.7cm and 517 grouped in DBTM > 1.7cm. Before propensity score matching, the 5-year recurrence-free survival was 38.7% in DBTM ≤ 1.7cm group and 67.1% in DBTM > 1.7cm (hazard ratio 0.48, P < 0.001), while the 5-year overall survival was 30.1% and 50.7%, respectively (hazard ratio 0.64, P < 0.001). After propensity score matching, the 5-year recurrence-free survival was 38.8%in DBTM ≤ 1.7cm group and66.1% in DBTM > 1.7cm (hazard ratio 0.51, P < 0.001), while the 5-year overall survival was34.7% and50%, respectively (hazard ratio 0.81, P = 0.012). Multivariable cox model showed that the DBTM was an independent predictor for recurrence-free survival (hazard ratio 0.51, P = 0.001) and overall survival (hazard ratio 0.84, P = 0.026). The DBTM was an independent predictor for outcomes in primary endobronchial neoplasm, and patients with the DBTM ≤ 1.7cm should actively receive adjuvant therapy after surgery. The distance between tumor and bronchial resection margin (DBTM), the distance between the most proximal border of the macroscopic tumor and bronchial resection margin was measured by pathologist in the fresh specimens before formalin fixation. The DBTM less than 1.7cm had higher recurrence-free survival and overall survival and was an independent prognostic factor for patients with primary endobronchial neoplasm.

An invasive zone in human liver cancer identified by Stereo-seq promotes hepatocyte–tumor cell crosstalk, local immunosuppression and tumor progression

Dissecting and understanding the cancer ecosystem, especially that around the tumor margins, which have strong implications for tumor cell infiltration and invasion, are essential for exploring the mechanisms of tumor metastasis and developing effective new treatments. Using a novel tumor border scanning and digitization model enabled by nanoscale resolution-SpaTial Enhanced REsolution Omics-sequencing (Stereo-seq), we identified a 500 µm-wide zone centered around the tumor border in patients with liver cancer, referred to as “the invasive zone”. We detected strong immunosuppression, metabolic reprogramming, and severely damaged hepatocytes in this zone. We also identified a subpopulation of damaged hepatocytes with increased expression of serum amyloid A1 and A2 (referred to collectively as SAAs) located close to the border on the paratumor side. Overexpression of CXCL6 in adjacent malignant cells could induce activation of the JAK-STAT3 pathway in nearby hepatocytes, which subsequently caused SAAs’ overexpression in these hepatocytes. Furthermore, overexpression and secretion of SAAs by hepatocytes in the invasive zone could lead to the recruitment of macrophages and M2 polarization, further promoting local immunosuppression, potentially resulting in tumor progression. Clinical association analysis in additional five independent cohorts of patients with primary and secondary liver cancer (n = 423) showed that patients with overexpression of SAAs in the invasive zone had a worse prognosis. Further in vivo experiments using mouse liver tumor models in situ confirmed that the knockdown of genes encoding SAAs in hepatocytes decreased macrophage accumulation around the tumor border and delayed tumor growth. The identification and characterization of a novel invasive zone in human cancer patients not only add an important layer of understanding regarding the mechanisms of tumor invasion and metastasis, but may also pave the way for developing novel therapeutic strategies for advanced liver cancer and other solid tumors.

Gold Nanostars Obviate Limitations to Laser Interstitial Thermal Therapy (LITT) for the Treatment of Intracranial Tumors.

Laser interstitial thermal therapy (LITT) is an effective minimally invasive treatment option for intracranial tumors. Our group produced plasmonics-active gold nanostars (GNS) designed to preferentially accumulate within intracranial tumors and amplify the ablative capacity of LITT. The impact of GNS on LITT coverage capacity was tested in ex vivo models using clinical LITT equipment and agarose gel-based phantoms of control and GNS-infused central "tumors." In vivo accumulation of GNS and amplification of ablation were tested in murine intracranial and extracranial tumor models followed by intravenous GNS injection, PET/CT, two-photon photoluminescence, inductively coupled plasma mass spectrometry (ICP-MS), histopathology, and laser ablation. Monte Carlo simulations demonstrated the potential of GNS to accelerate and specify thermal distributions. In ex vivo cuboid tumor phantoms, the GNS-infused phantom heated 5.5× faster than the control. In a split-cylinder tumor phantom, the GNS-infused border heated 2× faster and the surrounding area was exposed to 30% lower temperatures, with margin conformation observed in a model of irregular GNS distribution. In vivo, GNS preferentially accumulated within intracranial tumors on PET/CT, two-photon photoluminescence, and ICP-MS at 24 and 72 hours and significantly expedited and increased the maximal temperature achieved in laser ablation compared with control. Our results provide evidence for use of GNS to improve the efficiency and potentially safety of LITT. The in vivo data support selective accumulation within intracranial tumors and amplification of laser ablation, and the GNS-infused phantom experiments demonstrate increased rates of heating, heat contouring to tumor borders, and decreased heating of surrounding regions representing normal structures.

Intraoperative computed tomography perfusion navigation for maximal resection of high grade gliomas: a prospective non-randomized trial

Background: The main purpose of surgery for glioblastoma is to ensure the maximally possible cytoreduction. Computed tomography perfusion imaging has non-invasive tools for assessment of tumor blood flow and allows for visualization of the tumor borders and its most malignant zones.&#x0D; Aim: To evaluate the efficacy of intraoperative computed tomography perfusion navigation (ICTPN) during surgery for high grade gliomas.&#x0D; Materials and methods: This prospective non-randomized study included 142 patients (76 men and 66 women) with morphologically verified diagnosis of glioblastoma or diffuse astrocytoma grade 4 (World Health Organization 2021 criteria), who had surgery from 2016 to 2022. The ICTPN-based procedures were performed in 94 patients, with 55 with gross total and 39 with subtotal tumor resection. The control group included 48 patients with non-ICTPN-based surgical procedures. All patients were treated with standard adjuvant chemoradiation therapy. The efficacy of surgery was assessed every 3 months. The study endpoint was any tumor progression. The duration of the follow-up was 15 months. Baseline and contrast-enhanced preoperative imaging and postoperative follow-up assessments were performed with a 3T magnetic resonance imaging scanner (General Electric Discovery W750). ICTPN was done with a 32 slice computed tomography scanner (Toshiba Aquilion LB).&#x0D; Results: In the totally resected ICTPN group, the mean duration of the relapse-free period was 13.05 months; the relapse-free survival at 6 and 12 months was 92 and 55%, respectively (p 0.001). These results were significantly better than those in the subtotally resected ICTPN patients (8.98 months, 66 and 9%, respectively; log rank test for Kaplan-Meier curves, p 0.001) and in non-ICTPN patients (5.81 months, 23 and 0%, respectively, log rank test, p 0.001).&#x0D; Conclusion: ICTPN enables a more objective assessment of the tumor borders and the extent of its resection, as well as relapse-free survival benefits for the patients.

Intra- and peri-tumoral radiomics based on dynamic contrast-enhanced MRI for prediction of benign disease in BI-RADS 4 breast lesions: A multicentre study.

e13542 Background: The study aimed to develop and optimize a radiomics model with features extracted from breast intra- and peri-tumoral region in dynamic contrast-enhanced (DCE) MRI to distinguish benign from malignant breast lesions of Breast Imaging Reporting and Data System (BI-RADS) 4, thereby obviating unnecessary biopsies. Methods: We retrospectively analyzed data of women with BI-RADS 4 or 5 lesions from three hospitals. The regions of interest (ROIs) of intra-tumoral regions were delineated manually on each slice of image. The peri-tumoral regions were then obtained by equidistant 3-dimensinal dilation of the tumor border with 1, 2 and 3mm, respectively. Seven classification models were built with features extracted from the intra- and peri-tumoral regions, including the Intra, Peri1mm, Peri2mm, Peri3mm, Intra+peri1mm, Intra+peri2mm and Intra+peri3mm. Diagnostic performance was evaluated by the area under the receiver operating characteristic curve (AUC) and compared by DeLong test. Subgroup analysis was performed after stratifying all lesions by enhancement pattern. To assess the rate of avoidable biopsies, three exploratory cutoff values on the ROC curve were examined. Results: The Comb2 model, built with features from peri-tumoral 2mm and intra-tumoral region, demonstrated the best performance with AUCs of 0·901 and 0·863 in the development and external test cohort, respectively. The Comb2 model was robust in both mass and non-mass enhancement lesions. At the three exploratory cutoff values on the ROC curve, the model identified 11·2% (sensitivity of C1≥90%), 49·5% (sensitivity of C2≥95%) and 63·3% (sensitivity of C3≥98%) of the benign lesions in the development cohort. Applying the identified cutoff values in the external test cohort showed the potential to lower the number of unnecessary biopsies of benign lesions. Conclusions: An MRI-based radiomics model built with features extracted from the intra-tumoral region combined with the peri-tumoral 2mm showed the best potential to reduce false-positive diagnoses and may avoid unnecessary biopsies with a low underestimate risk.

Fully Automated Tumor Bud Assessment in Hematoxylin and Eosin-Stained Whole Slide Images of Colorectal Cancer

Tumor budding (TB), the presence of single cells or small clusters of up to 4 tumor cells at the invasive front of colorectal cancer (CRC), is a proven risk factor for adverse outcomes. International definitions are necessary to reduce interobserver variability. According to the current international guidelines, hotspots at the invasive front should be counted in hematoxylin and eosin (H&E)-stained slides. This is time-consuming and prone to interobserver variability; therefore, there is a need for computer-aided diagnosis solutions. In this study, we report an artificial intelligence-based method for detecting TB in H&E-stained whole slide images. We propose a fully automated pipeline to identify the tumor border, detect tumor buds, characterize them based on the number of tumor cells, and produce a TB density map to identify the TB hotspot. The method outputs the TB count in the hotspot as a computational biomarker. We show that the proposed automated TB detection workflow performs on par with a panel of 5 pathologists at detecting tumor buds and that the hotspot-based TB count is an independent prognosticator in both the univariate and the multivariate analysis, validated on a cohort of n = 981 patients with CRC. Computer-aided detection of tumor buds based on deep learning can perform on par with expert pathologists for the detection and quantification of tumor buds in H&E-stained CRC histopathology slides, strongly facilitating the introduction of budding as an independent prognosticator in clinical routine and clinical trials.

Edge Creep: Increased Pigmentation at the Border of Choroidal Melanomas Treated with Plaque Brachytherapy

Introduction: There is an increase in pigmentation that occurs in many tumors following plaque brachytherapy for choroidal melanoma. Correctly distinguishing between increased pigment at the tumor border versus true growth is imperative. We performed a retrospective review of patients treated with I-125 brachytherapy for choroidal melanoma at our institution to study this phenomenon. Methods: Records were reviewed for all patients undergoing plaque brachytherapy for uveal melanoma for a 5-year period (N = 195). Patients with iris and anterior tumors were excluded. Tumors treated more than 31 days after presentation were excluded. Fundus images for patients with increased pigmentation at any of the borders of the tumor at 6-month follow-up that extended beyond the initial pigmented margin were included (N = 20; 8 F, 12 M). Imaging at the last follow-up was reviewed, and it was confirmed that all tumors involuted appropriately with no evidence of local recurrence. The date of initial exam, time to treatment, and follow-up interval were recorded for each included patient. Results: Twenty patients (10%) exhibited increased pigment deposition at any of the borders of the tumor at 6-month follow-up that extended beyond the initial pigmented margin. Average tumor thickness was 3.2 mm (1.3–5.1); average largest tumor basal diameter was 11.6 mm (7–15.5). Average time from diagnosis to treatment was 25 days (17–31). Average length of follow-up was 35 months (16–68). No patient developed recurrence during the duration of follow-up, and 1 patient had developed metastasis. Conclusion: We describe the phenomenon of increased pigment deposition, “edge creep,” at the borders of choroidal melanomas treated with plaque brachytherapy that gave the appearance of initial tumor growth but then subsequently remained stable over time. It is important that treating ocular oncologists be aware of this phenomenon to avoid unnecessary diagnosis of local recurrence.

Exploring Novel Innovation Strategies to Close a Technology Gap in Neurosurgery: HORAO Crowdsourcing Campaign

Scientific research is typically performed by expert individuals or groups who investigate potential solutions in a sequential manner. Given the current worldwide exponential increase in technical innovations, potential solutions for any new problem might already exist, even though they were developed to solve a different problem. Therefore, in crowdsourcing ideation, a research question is explained to a much larger group of individuals beyond the specialist community to obtain a multitude of diverse, outside-the-box solutions. These are then assessed in parallel by a group of experts for their capacity to solve the new problem. The 2 key problems in brain tumor surgery are the difficulty of discerning the exact border between a tumor and the surrounding brain, and the difficulty of identifying the function of a specific area of the brain. Both problems could be solved by a method that visualizes the highly organized fiber tracts within the brain; the absence of fibers would reveal the tumor, whereas the spatial orientation of the tracts would reveal the area's function. To raise awareness about our challenge of developing a means of intraoperative, real-time, noninvasive identification of fiber tracts and tumor borders to improve neurosurgical oncology, we turned to the crowd with a crowdsourcing ideation challenge. Our objective was to evaluate the feasibility of a crowdsourcing ideation campaign for finding novel solutions to challenges in neuroscience. The purpose of this paper is to introduce our chosen crowdsourcing method and discuss it in the context of the current literature. We ran a prize-based crowdsourcing ideation competition called HORAO on the commercial platform HeroX. Prize money previously collected through a crowdfunding campaign was offered as an incentive. Using a multistage approach, an expert jury first selected promising technical solutions based on broad, predefined criteria, coached the respective solvers in the second stage, and finally selected the winners in a conference setting. We performed a postchallenge web-based survey among the solvers crowd to find out about their backgrounds and demographics. Our web-based campaign reached more than 20,000 people (views). We received 45 proposals from 32 individuals and 7 teams, working in 26 countries on 4 continents. The postchallenge survey revealed that most of the submissions came from single solvers or teams working in engineering or the natural sciences, with additional submissions from other nonmedical fields. We engaged in further exchanges with 3 out of the 5 finalists and finally initiated a successful scientific collaboration with the winner of the challenge. This open innovation competition is the first of its kind in medical technology research. A prize-based crowdsourcing ideation campaign is a promising strategy for raising awareness about a specific problem, finding innovative solutions, and establishing new scientific collaborations beyond strictly disciplinary domains.

The efficacy of dermoscopy in defining the surgical margins of cutaneous squamous cell carcinoma: a retrospective study.

To investigate the diagnostic value of dermoscopy in defining the tumor margin of cutaneous squamous cell carcinoma (cSCC) for the appropriate surgical margin. A total of 90 cSCC patients were enrolled in the study. All patients were recruited into two groups: those who preserved intact macroscopic features of neoplasms without or after incisional biopsy and those with uncertain residual tumors after excisional biopsy. A dermoscopy-defined surgical margin of 8mm outward was used according to the tumor boundaries observed with the naked eye and dermoscopy. All excised tumor specimens were divided into serial sections according to the four "3, 6, 9, 12" directions at every 4-mm interval from the dermoscopy-detected tumor margin. Pathological examination was performed at 0mm, 4mm, and 8mm margins to confirm tumor remnants. Retrospective analysis of dermatoscopic results showed inconsistent clinical and dermatoscopic borders in 43 of 90 cases (47.8%). The ability of dermoscopy to detect tumor borders showed no statistical difference between the two groups (p > 0.05). In the unbiopsy or incisional biopsy group, 66.6% of the tumors were resected with a 4-mm margin and 98.3% with an 8-mm margin, with significant differences (p = 0.047). For patients with inconspicuous clinical evidence of residual tumor after excisional biopsy, the tumor clearance rate was 53.3% at 0mm, 93.3% at 4mm, and 100.0% at 8mm. Statistically significant differences were noted between 0mm and 4mm (p = 0.017), as well as between 0mm and 8mm (p = 0.043) but did not differ between 4mm and 8mm (p>0.05). Dermoscopy defined the tumor margin of cSCC better than visual inspection alone. Direct dermoscopic-guided surgery with at least 8-mm expansion was recommended for high-risk cSCC. Dermoscopy also assisted in identifying surgical margins at the healing biopsy site, making 8mm still the recommended expansion range.

Supratotal Surgical Resection for Low-Grade Glioma: A Systematic Review.

Low-grade gliomas (LGGs) are optimally treated with up-front maximal safe surgical resection, typically defined as maximizing the extent of tumor resection while minimizing neurologic risks of surgery. Supratotal resection of LGG may improve outcomes beyond gross total resection by removing tumor cells invading beyond the tumor border as defined on MRI. However, the evidence regarding supratotal resection of LGG, in terms of impact on clinical outcomes, such as overall survival and neurologic morbidities, remains unclear. Authors independently searched the PubMed, Medline, Ovid, CENTRAL (Cochrane Central Register of Controlled Trials), and Google Scholar databases for studies evaluating overall survival, time to progression, seizure outcomes, and postoperative neurologic and medical complications of supratotal resection/FLAIRectomy of WHO-defined LGGs. Papers in languages other than English, lacking full-text availability, evaluating supratotal resection of WHO-defined high-grade gliomas only, and nonhuman studies were excluded. After literature search, reference screening, and initial exclusions, 65 studies were screened for relevancy, of which 23 were evaluated via full-text review, and 10 were ultimately included in the final evidence review. Studies were evaluated for quality using the MINORS criteria. After data extraction, a total of 1301 LGG patients were included in the analysis, with 377 (29.0%) undergoing supratotal resection. The main measured outcomes were extent of resection, pre- and postoperative neurological deficits, seizure control, adjuvant treatment, neuropsychological outcomes, ability to return to work, progression-free survival, and overall survival. Overall, low- to moderate-quality evidence was supportive of aggressive, functional boundary-based resection of LGGs due to improvements in progression-free survival and seizure control. The published literature provides a moderate amount of low-quality evidence supporting supratotal surgical resection along functional boundaries for low-grade glioma. Among patients included in this analysis, the occurrence of postoperative neurological deficits was low, and nearly all patients recovered within 3 to 6 months after surgery. Notably, the surgical centers represented in this analysis have significant experience in glioma surgery in general, and supratotal resection specifically. In this setting, supratotal surgical resection along functional boundaries appears to be appropriate for both symptomatic and asymptomatic low-grade glioma patients. Larger clinical studies are needed to better define the role of supratotal resection in LGG.