Tumor Margin Research Articles

Abstract PO2-03-03: The Significance of Cavity Shave Margins in Breast Carcinoma on Margin Status and Re-excision Rates

Abstract Context: The comparative outcomes of breast conserving surgery (BCS) with and without cavity shave margins are not well established. We aim to evaluate the impact of each procedure on final margin status and rate of re-excision. Design: A total of 529 breast cancer cases from our institution between 2013-2015 were included. Demographic and clinicopathological data including procedure type, tumor type, grade, margins status, and re-excision rates were collected. H&E slides of positive margins (tumor on ink) were reviewed by two pathologists. Appropriate statistical analysis was performed. Results: Out of 529 breast cancer cases, 125 were Ductal Carcinoma in situ (DCIS), 152 were Invasive Ductal Carcinoma (IDC) and 252 had both pathologies. The median age of patients was 59 years (range: 24-90). Patients who underwent excision with shave margins were 162 (35 DCIS, 56 IDC, 71 both) while excision without shave margins were 367 (90 DCIS, 96 IDC, 181 both). Re-excision rates were significantly lower 1) in patients who underwent BCS with cavity shave margins compared to those without (OR 0.32, p< 0.001) and 2) in patients who did not require lymph node excision compared to those who did (OR 4.26, p< 0.001). Additionally, patients who had DCIS had a higher rate of re-excision than those with invasive cancer only (OR 5.17, P< .001). After adjusting for type of tumor, patients who underwent cavity shaving compared to those who did not, no significant difference was seen in tumor at margins (OR 0.73, p=0.282) or tumor within 2mm (OR 1.14, p=0.512) from margins. However, patients with IDC who underwent cavity shave had a higher proportion of negative tumor at the margins (76.5% vs. 67.0%; p=0.051). We found that patients who had an invasive carcinoma (IC) had a lower risk of having tumor at the margin or within 2 mm from the margin than those with DCIS or DCIS+IC, (p< .05). Conclusions: Our data shows that BCS with cavity shave margins is superior with regards to negative margin and re-excision rates when compared to without cavity shave margins. Citation Format: Fadi Zaiem, Anna Numi, Mira Kheil, Asem AbuJamea, Deepti Jain, Omar Abbas, Lauren Larson, Noor Suleiman, Saleh Al-Juburi, Sanaa Awada, Ragad Almsaddi, Hyejeong Jang, Seongho Kim, Nagla Salem, Lydia Choi, Sudeshna Bandyopadhyay, Sunil Jaiman, Rouba Ali-Fehmi. The Significance of Cavity Shave Margins in Breast Carcinoma on Margin Status and Re-excision Rates [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-03-03.

Abstract PO4-07-08: Impact of an MRI/US fusion imaging for preoperative planning using non-wire localization technique in breast conserving surgery in patients with non-mass enhancement on MRI. A prospective multicenter study

Abstract [Background] Preoperative breast MRI is used to evaluate for additional and extent disease for newly diagnosed breast cancer patients with dense breasts. The potential benefit of preoperative MRI is still being controversial. However, when breast conserving surgery (BCS) is considered for non-mass enhancement (NME) on MRI, the precise image-guided localization is required. Although breast ultrasound (US) plays an adjunctive role in evaluation of MRI findings in preoperative planning for BCS, NME is less likely than a mass or focus to have a US correlate. Furthermore, the presence of NME increases the re-operation rate in BCS because of the difficulty in evaluating the tumor margin. An MRI/US fusion imaging has recently been developed that uses either real-time virtual sonography TM (RVS) or volume navigation TM (Vnav), and can overlay an US with the MRI image of the same site in real time by using magnetic position tracking system. The purpose of this prospective multicenter study was to evaluate the effect of MRI/US fusion imaging for preoperative planning using non-wire localization technique in BCS in patients with NME. [Methods] In 3 Japanese hospital, 13 patients who had lesions with NME that exceeded the US hypoechoic area were enrolled in this study from 2019 to 2022. Written informed consent was acquired, and then an additional supine MRI using a body surface coil was performed. During preoperative planning before BCS, RVS/Vnav was used to determine the NME enhancing area and to mark the area on the skin. Tissue markers were inserted under US at a location assessed by RVS/Vnav as the edge of extent of NME. We analyzed both the surgical margin positivity rate and the reoperation rate. [Results] The preoperative diagnosis by core needle biopsy were 6 DCIS and 7 invasive ductal carcinoma. NME distribution types were 7 segmental, 3 focal, 2 linear 4 and 1 regional. The median diameters of the NME and hypo-echoic lesions were 31 mm (range: 18–39 mm) and 16 mm (range: 9–32 mm), respectively (p = 0.0005). After confirming the localization of the tissue marker with intraoperative US, 12 lumpectomy and 1 quadrantectomy were conducted. The median specimen weight was 63g (range: 54-105g). In the final pathologic diagnosis of excised specimens were 5 DCIS and 8 IDC. In 8 cases (62%), the pathologic diameter was larger than the US diameter. All surgical margins were negative. None of the patients required additional resection. [Conclusions] The findings of study suggest that preoperative planning using non-wire localization technique under MRI/US fusion imaging for BCS in patients with NME could improve both a surgical margin positive rate and a reoperation rate. Citation Format: Shogo Nakano, Manabu Futamura, Keitaro Kamei, Takayoshi Uematsu, Miwa Yoshida, Sadako Akashi-Tanaka, Junta Sakakibara, Ichiro Isomoto, Hiroko Satake, Maiko Takahashi, Minami Hatono, Junko Araki. Impact of an MRI/US fusion imaging for preoperative planning using non-wire localization technique in breast conserving surgery in patients with non-mass enhancement on MRI. A prospective multicenter study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-07-08.

Abstract PO2-28-11: How to improve margins in breast cancer surgery: a

Abstract Objective: Intraoperative specimen mammography (ISM) is a diffuse technique that allows surgeons to check specimens immediately after lumpectomy, instead of intraoperative frozen sections, definitely abandoned. in Italy and Europe, because it is regarded as too expensive and time-consuming examination. Although the specimen is slightly compressed, the radiological image can be distorted by tissue overlap, and this may affect the evaluation of tumor borders, resulting in extension of the lumpectomy. As ISM may be less precise due to inadequate compression, a vacuum effect was applied to the specimen to increase the precision of margin detection. Study design: This study was conducted at St. Anna Hospital Breast Unit, Turin, Italy. Women who underwent lumpectomy for cancer were eligible for inclusion. BCS resection was performed with a free margin, and the surgical specimen was imaged immediately by SSM and evaluated by an expert radiologist and surgeon.Inclusion criteria were: breast cancer detected by a screening test, and treatment with surgical lumpectomy. Both standard ISM (sISM) and vacuum ISM (vISM) were performed. A dedicated breast surgeon at the study institution performed both surgery and radiological scans, and their interpretation. A dedicated radiologist reviewed all of the images. ISM was performed by a digital specimen mammography system (Faxitron, Bioptics Inc., Tucson, AZ, USA) in the operating room. Specimen registration and ISM analysis took 3 min. sISM (two orthogonal projections) was performed. Specimens were sealed in plastic bags in the vacuum apparatus (TissueSAFE Milestone Medical, Sorisole, Italy); this process took a few seconds. 152 specimens obtained after lumpectomy from 1 April 2021 to 31 April 2022 were scanned. sISM (two orthogonal projections) was performed. Next, the specimen was placed in a vacuum bag, and vISM was performed. Additional tissue was removed if the surgeon considered that excision was inadequate. Finally, the specimen was sent for definitive histopathological analysis, which is the gold standard for the assessment of surgical margins. Intraoperative histological margin assessment was not performed. The sISM and vISM images and final histopathology reports were compared. A first experience on a limited number of patients to demonstrate feasibility of the technique, is reported in table 1 and 2. Results: For sISM, specificity was 43,85% [95 % confidence interval (CI) 35.96-51.73], sensitivity was 40.91% (95 % CI 33.09-48.73), positive predictive value (PPV) 10.98% (95 % CI 6.01-15.95) and negative predictive value (NPV) 81.43% (95 % CI 75.25-87.61). For vISM, specificity 92,31% (95 % CI 88,07-96.54), sensitivity 72.73% (95 % CI 65.65-79.81), PPV 61.54% (95 % CI 53.80-69.27) and NPV 95.24% (95 % CI 91.85-98.62). Conclusion: ISM is a valid, safe and quicker alternative to intraoperative histopathological study, but has been reported to be limited due to less compression than standard SSM. Consequently, ISM may result in a high percentage of false-positive results, meaning unnecessary wider resections that lead to increased operative times and worse aesthetic results. A vacuum effect was performed on the specimen to increase the precision of margin detection. vISM images seem to be easier to interpret than sISM images (Figs. 1–3) as they are characterized by a vacuum-created radiolucent rim that better defines the tumor margins. These data suggest that the vacuum technique is feasible, cost-saving and yields results that are similar to those from frozen sections but without the limitations, such as prolonged operating time, high variability in sensitivity due to pathologists abilities, risk of compromising the histology, and unreliability for small lumps and ductal carcinoma in situ. Keywords: Breast cancer; Intraoperative mammography; Lumpectomy; Specimen mammography; Vacuum intraoperative mammography. Table 1. Clinical Data IC, invasive cancer; DCIS ductal carcinoma in situ; ADH, atypical ductal hyperplasia; ILC, invasive lobular cancer; B3, lesions of uncertain malignant potential; IMPC, invasive micropapillary carcinoma; NST, no special type; sISM, standard intraoperative specimen mammography; vISM, vacuum intraoperative specimen mammography. ª Margin: 0, involved; 1, free Table 2. Figure 1 - 2 - 3 Standard intraoperative specimen mammography (left) and vacuum intraoperative specimen mammography (right). Citation Format: Maria Grazia Baù, Vincenzo Marra, Alessandra Surace, Donatella Tota, Maria Piera Mano, Aurelia Mondino, Alessandro Bottero, Elisabetta Robba. How to improve margins in breast cancer surgery: a [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-28-11.

Microscope-integrated optical coherence tomography for in vivo human brain tumor detection with artificial intelligence.

It has been shown that optical coherence tomography (OCT) can identify brain tumor tissue and potentially be used for intraoperative margin diagnostics. However, there is limited evidence on its use in human in vivo settings, particularly in terms of its applicability and accuracy of residual brain tumor detection (RTD). For this reason, a microscope-integrated OCT system was examined to determine in vivo feasibility of RTD after resection with automated scan analysis. Healthy and diseased brain was 3D scanned at the resection edge in 18 brain tumor patients and investigated for its informative value in regard to intraoperative tissue classification. Biopsies were taken at these locations and labeled by a neuropathologist for further analysis as ground truth. Optical OCT properties were obtained, compared, and used for separation with machine learning. In addition, two artificial intelligence-assisted methods were utilized for scan classification, and all approaches were examined for RTD accuracy and compared to standard techniques. In vivo OCT tissue scanning was feasible and easily integrable into the surgical workflow. Measured backscattered light signal intensity, signal attenuation, and signal homogeneity were significantly distinctive in the comparison of scanned white matter to increasing levels of scanned tumor infiltration (p < 0.001) and achieved high values of accuracy (85%) for the detection of diseased brain in the tumor margin with support vector machine separation. A neuronal network approach achieved 82% accuracy and an autoencoder approach 85% accuracy in the detection of diseased brain in the tumor margin. Differentiating cortical gray matter from tumor tissue was not technically feasible in vivo. In vivo OCT scanning of the human brain has been shown to contain significant value for intraoperative RTD, supporting what has previously been discussed for ex vivo OCT brain tumor scanning, with the perspective of complementing current intraoperative methods for this purpose, especially when deciding to withdraw from further resection toward the end of the surgery.

Supramarginal resection of skull base chordomas: proof of concept and preliminary outcomes.

The mainstay of treatment for skull base chordoma (SBC) is maximal safe resection followed by radiotherapy. However, even after gross-total resection (GTR), the recurrence rate is high due to microscopic disease in the resection margins. Therefore, supramarginal resection (SMR) could be beneficial, as has been shown for sacral chordoma. The paradigm of postoperative radiation therapy for every patient has also begun to change, as molecular profiling has shown variability in the risk of recurrence. The aim of this study was to present the concept of SMR applied to SBC, along with an individualized decision for postoperative radiation therapy. This is a retrospective analysis of all SBCs operated on by the senior author between 2018 and 2023. SMR was defined as negative histological margins of bone and/or dura mater, along with evidence of bone resection beyond the tumor margins in the craniocaudal and lateral planes on postoperative imaging. Tumors were classified into 3 molecular recurrence risk groups (group A, low risk; group B, intermediate risk; and group C, high risk). Postoperative radiation therapy was indicated in group C tumors, in group B chordomas without SMR, or in cases of patient preference. Twenty-two cases of SBC fulfilled the inclusion criteria. SMR was achieved in 12 (55%) cases, with a mean (range) amount of bone resection beyond the tumor margins of 10 (2-20) mm (+40%) in the craniocaudal axis and 6 (1-15) mm (+31%) in the lateral plane. GTR and near-total resection were each achieved in 5 (23%) cases. Three (19%) tumors were classified as group A, 12 (75%) as group B, and 1 (6%) as group C. Although nonsignificant due to the small sample size, the trends showed that patients in the SMR group had smaller tumor volumes (13.9 vs 19.6 cm3, p = 0.35), fewer previous treatments (33% vs 60% of patients, p = 0.39), and less use of postoperative radiotherapy (25% vs 60%, p = 0.19) compared to patients in the non-SMR group. There were no significant differences in postoperative CSF leak (0% vs 10%, p = 0.45), persistent cranial nerve palsy (8% vs 20%, p = 0.57), and tumor recurrence (8% vs 10%, p = 0.99; mean follow-up 15 months) rates between the SMR and non-SMR groups. In select cases, SMR of SBC appears to be feasible and safe. Larger cohorts and longer follow-up evaluations are necessary to explore the benefit of SMR and individualized postoperative radiation therapy on progression-free survival.

Rapid evaporative ionization mass spectrometry: A survey through 15 years of applications.

Rapid evaporative ionization mass spectrometry (REIMS) is a relatively recent MS technique explored in many application fields, demonstrating high versatility in the detection of a wide range of chemicals, from small molecules (phenols, amino acids, di- and tripeptides, organic acids, and sugars) to larger biomolecules, that is, phospholipids and triacylglycerols. Different sampling devices were used depending on the analyzed matrix (liquid or solid), resulting in distinct performances in terms of automation, reproducibility, and sensitivity. The absence of laborious and time-consuming sample preparation procedures and chromatographic separations was highlighted as a major advantage compared to chromatographic methods. REIMS was successfully used to achieve a comprehensive sample profiling according to a metabolomics untargeted analysis. Moreover, when a multitude of samples were available, the combination with chemometrics allowed rapid sample differentiation and the identification of discriminant features. The present review aims to provide a survey of literature reports based on the use of such analytical technology, highlighting its mode of operation in different application areas, ranging from clinical research, mostly focused on cancer diagnosis for the accurate identification of tumor margins, to the agri-food sector aiming at the safeguard of food quality and security.

Optimizing Treatment Quality in Head and Neck Cancer Therapy: Impact of Adaptive Intensity-Modulated Radiotherapy on Plan Quality and Tumor Volume Changes

Objective: This research analyses whether volumetric changes and PTV shifting affect adaptive intensity-modulated radiotherapy (IMRT) plan quality and head and neck cancer therapy. Methods: The research was carried out at the Sohag Cancer Centre in Egypt, including a sample of 36 individuals diagnosed with head and neck squamous cell carcinoma (HNSCC). Patients were chosen on the basis of the following criteria: locally progressed and node-positive malignancy, oropharyngeal cancer, oral cavity cancer, and unknown primary. The research used dynamic intensity-modulated radiation therapy (D-IMRT) to establish treatment plans and Siemens SOMATOM DEFINITION CT scanners to acquire 3D anatomical images. A range of 1.64 to 2.12 Gy was observed for the median dosage per fraction. Using the conformance index (CI) and the homogeneity index, the quality of the plan was assessed (HI). The threshold for statistical significance was set at 0.05. Results: The study analysed patients with unilateral and bilateral HNSCC tumors, with a majority having bilateral tumors. The findings demonstrated that the tumor PTV was significantly reduced as a consequence of the suggested adaptive radiation techniques. Both the homogeneity index and the conformity index were used to evaluate the plan's quality (HI). The maximal homogeneity index (HI) was reached after 7 and 14 fractions, respectively. The positive correlation between PTV reduction and CI after 7 fractions, while a negative correlation found after fractions 14 and 21. It was also shown that HI is positively correlated with PTV changes after 7 and 14. Conclusion: The use of adaptive radiotherapy in intensity-modulated radiation therapy (IMRT) treatment planning improves plan quality and decreases error rates due to tumor margin movement. Following radiation fractions, PTV shifting affects the homogeneity index (HI).

Advanced diffusion MRI provides evidence for altered axonal microstructure and gradual peritumoral infiltration in GBM in comparison to brain metastases

PurposeIn contrast to peritumoral edema in metastases, GBM is histopathologically characterized by infiltrating tumor cells within the T2 signal alterations. We hypothesized that depending on the distance from the outline of the contrast-enhancing tumor we might reveal imaging evidence of gradual peritumoral infiltration in GBM and predominantly vasogenic edema around metastases. We thus investigated the gradual change of advanced diffusion metrics with the peritumoral zone in metastases and GBM.MethodsIn 30 patients with GBM and 28 with brain metastases, peritumoral T2 hyperintensity was segmented in 33% partitions based on the total volume beginning at the enhancing tumor margin and divided into inner, middle and outer zones. Diffusion Tensor Imaging (DTI)-derived fractional anisotropy and mean diffusivity as well as Diffusion Microstructure Imaging (DMI)-based parameters Dax-intra, Dax-extra, V‑CSF and V-intra were employed to assess group-wise differences between inner and outer zones as well as within-group gradients between the inner and outer zones.ResultsIn metastases, fractional anisotropy and Dax-extra were significantly reduced in the inner zone compared to the outer zone (FA p = 0.01; Dax-extra p = 0.03). In GBM, we noted a reduced Dax-extra and significantly lower intraaxonal volume fraction (Dax-extra p = 0.008, V‑intra p = 0.006) accompanied by elevated axial intraaxonal diffusivity in the inner zone (p = 0.035). Between-group comparison of the outer to the inner zones revealed significantly higher gradients in metastases over GBM for FA (p = 0.04) as well as the axial diffusivity in the intra- (p = 0.02) and extraaxonal compartment (p < 0.001).ConclusionOur findings provide evidence of gradual alterations within the peritumoral zone of brain tumors. These are compatible with predominant (vasogenic) edema formation in metastases, whereas our findings in GBM are in line with an axonal destructive component in the immediate peritumoral area and evidence of tumor cell infiltration with accentuation in the tumor’s vicinity.

Clinical Theranostics in Recurrent Gliomas: A Review.

Gliomas represent the most commonly occurring tumors in the central nervous system and account for approximately 80% of all malignant primary brain tumors. With a high malignancy and recurrence risk, the prognosis of high-grade gliomas is poor, with a mean survival time of 12-18 months. While contrast-enhanced MRI serves as the standard diagnostic imaging modality for gliomas, it faces limitations in the evaluation of recurrent gliomas, failing to distinguish between treatment-related changes and tumor progression, and offers no direct therapeutic options. Recent advances in imaging modalities have attempted to address some of these limitations, including positron emission tomography (PET), which has demonstrated success in delineating tumor margins and guiding the treatment of recurrent gliomas. Additionally, with the advent of theranostics in nuclear medicine, PET tracers, when combined with therapeutic agents, have also evolved beyond a purely diagnostic modality, serving both diagnostic and therapeutic roles. This review will discuss the growing involvement of theranostics in diagnosing and treating recurrent gliomas and address the associated impact on quality of life and functional recovery.

MOHS SURGERY

Mohs surgery is a highly specialized procedure used to treat skin cancer, especially basal cell carcinoma and squamous cell carcinoma. This technique is known for its high cure rate and preservation of healthy tissue around the affected area. This study aims to review and address the most recent updates in the Mohs surgery technique, including advances in equipment and instruments, improved treatment protocols and post-surgical reconstruction techniques, while also discussing the growing importance of this procedure in contemporary dermatological practice and its positive impact on patients’ quality of life. Mohs surgery involves the surgical removal of thin layers of cancerous tissue, followed by immediate microscopic analysis of the margins of the removed tissue. This allows precise identification of the tumor margins, ensuring complete removal of the cancer while preserving as much healthy tissue as possible. Recent updates to the technique include the use of advanced imaging techniques, such as dermoscopy and confocal microscopy, to aid in the precise identification of tumor margins prior to surgery. In addition, the development of more effective surgical reconstruction methods has improved aesthetic and functional results for patients. It is therefore concluded that Mohs surgery remains an effective option for the treatment of skin cancer, offering high cure rates and preservation of healthy tissue. Updates to the technique, including improvements in diagnostic accuracy and reconstruction options, have contributed to increasingly better results for patients undergoing this procedure.

Correlation analysis between BRAFV600E mutation and ultrasonic and clinical features of papillary thyroid cancer

PurposeThe study investigates the value of the BRAFV600E mutation in determining the aggressiveness of papillary thyroid cancer (PTC) and its correlation with ultrasound features. MethodsThe study selected 176 patients with BRAFV600E mutation and 80 without the mutation who underwent surgery at Guangxi Medical University Cancer Hospital. Clinical and pathological data were collected, focusing on BRAFV600E mutations and associated ultrasonic features. Correlation analysis, as well as univariate and multivariate logistic regression analysis, were conducted to identify independent risk factors for BRAFV600E mutation. The results were verified using a nomogram model. ResultsThe analysis results indicate that the BRAFV600E mutation correlates with tumor size, nodule size, taller-than-wide shape, margin, and shape of papillary thyroid cancer. The receiver operating characteristic curve was used to analyze the diagnostic effect of these features on BRAFV600E mutation. The results showed that nodule size had the most significant area under the curve (AUC = 0.665). Univariate and multivariate logistic regression analyses revealed that taller-than-wide shape ≥1, ill-defined margin, irregular shape, nodule size (≤1.40 cm), TT4 (>98.67 nmol/L), and FT3 (<4.14 pmol/L) were independent risk factors for BRAFV600E mutation. While considering all these factors in the nomogram, the Concordance index (C-index) remained high at 0.764. This suggests that the model has a good predictive effect. ConclusionUltrasound features including nodule size, taller-than-wide shape ≥1, ill-defined margins, irregular shape, higher TT4 levels, and lower FT3 levels were associated with papillary thyroid cancer aggressiveness and BRAFV600E mutation.

Virtual tumor mapping and margin control with 3-D planning and navigation.

Computer technology-based treatment approaches like intraoperative navigation and intensity-modulated radiation therapy have become important components of state of the art head and neck cancer treatment. Multidirectional exchange of virtual three-dimensional patient data via an interdisciplinary platform allows all medical specialists involved in the patients treatment to take full advantage of these technologies. This review article gives an overview of current technologies and future directions regarding treatment approaches that are based on a virtual, three-dimensional patient specific dataset: storage and exchange of spatial information acquired via intraoperative navigation allow for a highly precise frozen section procedure. In the postoperative setting, virtual reconstruction of the tumor resection surface provides the basis for improved radiation therapy planning and virtual reconstruction of the tumor with integration of molecular findings creates a valuable toolfor postoperative treatment and follow-up. These refinements of established treatment components and novel approaches have the potential to make a major contribution to improving the outcome in head and neck cancer patients.

Multivariate mapping of low-resilient neurocognitive systems within and around low-grade gliomas.

Accumulating evidence suggests that the brain exhibits a remarkable capacity for functional compensation in response to neurological damage, a resilience potential that is deeply rooted in the malleable features of its underlying anatomofunctional architecture. This propensity is particularly exemplified by diffuse low-grade glioma, a subtype of primary brain tumour. However, functional plasticity is not boundless, and surgical resections directed at structures with limited neuroplasticity can lead to incapacitating impairments. Yet, maximizing diffuse low-grade glioma resections offers substantial oncological benefits, especially when the resection extends beyond the tumour margins (i.e. supra-tumour or supratotal resection). In this context, the primary objective of this study was to identify which cerebral structures were associated with less favourable cognitive outcomes after surgery, while accounting for intra-tumour and supra-tumour features of the surgical resections. To achieve this objective, we leveraged a unique cohort of 400 patients with diffuse low-grade glioma who underwent surgery with awake cognitive mapping. Patients benefitted from a neuropsychological assessment consisting of 18 subtests administered before and 3 months after surgery. We analysed changes in performance and applied topography-focused and disconnection-focused multivariate lesion-symptom mapping using support vector regressions, in an attempt to capture resected cortico-subcortical structures less amenable to full cognitive compensation. The observed changes in performance were of a limited magnitude, suggesting an overall recovery (13 of 18 tasks recovered fully despite a mean resection extent of 92.4%). Nevertheless, lesion-symptom mapping analyses revealed that a lack of recovery in picture naming was linked to damage in the left inferior temporal gyrus and inferior longitudinal fasciculus. Likewise, for semantic fluency abilities, an association was established with damage to the left precuneus/posterior cingulate. For phonological fluency abilities, the left dorsomedial frontal cortex and the frontal aslant tract were implicated. Moreover, difficulties in spatial exploration were associated with injury to the right dorsomedial prefrontal cortex and its underlying connectivity. An exploratory analysis suggested that supra-tumour resections were associated with a less pronounced recovery following specific resection patterns, such as supra-tumour resections of the left uncinate fasciculus (picture naming), the left corticostriatal tract and the anterior corpus callosum (phonological fluency), the hippocampus and parahippocampus (episodic memory) and the right frontal-mesial areas (visuospatial exploration). Collectively, these patterns of results shed new light on both low-resilient neural systems and the prediction of cognitive recovery following glioma surgery. Furthermore, they indicate that supra-tumour resections were only occasionally less well tolerated from a cognitive viewpoint. In doing so, they have deep implications for surgical planning and rehabilitation strategies.

An assessment of risk factors for recurrence and survival for patients undergoing liver resection for intrahepatic cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (iCCA) is the second most common primary liver malignancy with increasing rates of incidence and mortality. Surgical resection is curative for patients who are diagnosed at early stages of iCCA. Limited data exist regarding risk factors for postresection recurrence and overall survival as iCCA is rare, and majority of patients are diagnosed at an advanced stage and thus not candidates for resection. We aimed to analyze clinical and laboratory characteristics, tumor histology, locoregional invasion, recurrence and survival in patients undergoing curative resection for iCCA. All patients who underwent curative resection for iCCA between 2006 and 2023 at our institution were included in the study. Clinical characteristics, laboratory, histological and follow-up data were collected. The 1-, 3-, and, 5-year survival rates were 90.9%, 65.9% and 44.2%, respectively. About 65.6% of patients had recurrence in a median of 1.2 years after liver resection. Positive surgical margins were present in 20.73% of patients. Notably, 80.51% had solitary tumor and the remaining 19.48% had multifocal tumor. A total of 64.51% of patients received adjuvant chemotherapy after resection. A total of 26 (31.3%) patients had died during the follow-up period. Duration from liver resection to last follow-up or death was 1.6 years (0.8-3.2). Overall median survival was 4.6 years. The presence of lymph node metastases, vascular invasion, positive surgical margin and advanced tumor stage at diagnosis were associated with significantly worse overall survival, which remained significant in multivariable model for advanced tumor stage and positive surgical margin. Despite curative resection, recurrence rate is high and overall survival is poor in patients with iCCA. Real-world data regarding patient characteristics and longitudinal follow-up remain important as iCCA is a rare malignancy.

Diagnostic Model for Proliferative HCC Using LI-RADS: Assessing Therapeutic Outcomes in Hepatectomy and TKI-ICI Combination.

Proliferative hepatocellular carcinoma (HCC), aggressive with poor prognosis, and lacks reliable MRI diagnosis. To develop a diagnostic model for proliferative HCC using liver imaging reporting and data system (LI-RADS) and assess its prognostic value. Retrospective. 241 HCC patients underwent hepatectomy (90 proliferative HCCs: 151 nonproliferative HCCs), divided into the training (N = 167) and validation (N = 74) sets. 57 HCC patients received combination therapy with tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs). 3.0 T, T1- and T2-weighted, diffusion-weighted, in- and out-phase, T1 high resolution isotropic volume excitation and dynamic gadoxetic acid-enhanced imaging. LI-RADS v2018 and other MRI features (intratumoral artery, substantial hypoenhancing component, hepatobiliary phase peritumoral hypointensity, and irregular tumor margin) were assessed. A diagnostic model for proliferative HCC was established, stratifying patients into high- and low-risk groups. Follow-up occurred every 3-6 months, and recurrence-free survival (RFS), progression-free survival (PFS) and overall survival (OS) in different groups were compared. Fisher's test or chi-square test, t-test or Mann-Whitney test, logistic regression, Harrell's concordance index (C-index), Kaplan-Meier curves, and Cox proportional hazards. Significance level: P < 0.05. The diagnostic model, incorporating corona enhancement, rim arterial phase hyperenhancement, infiltrative appearance, intratumoral artery, and substantial hypoenhancing component, achieved a C-index of 0.823 (training set) and 0.804 (validation set). Median follow-up was 32.5 months (interquartile range [IQR], 25.1 months) for postsurgery patients, and 16.8 months (IQR: 13.2 months) for combination-treated patients. 99 patients experienced recurrence, and 30 demonstrated tumor nonresponse. Differences were significant in RFS and OS rates between high-risk and low-risk groups post-surgery (40.3% vs. 65.8%, 62.3% vs. 90.1%, at 5 years). In combination-treated patients, PFS rates differed significantly (80.6% vs. 7.7% at 2 years). The MR-based model could pre-treatment identify proliferative HCC and assist in prognosis evaluation. Stage 2.

MRI-based clinical-radiomics nomogram model for predicting microvascular invasion in hepatocellular carcinoma.

Preoperative microvascular invasion (MVI) of liver cancer is an effective method to reduce the recurrence rate of liver cancer. Hepatectomy with extended resection and additional adjuvant or targeted therapy can significantly improve the survival rate of MVI+ patients by eradicating micrometastasis. Preoperative prediction of MVI status is of great clinical significance for surgical decision-making and the selection of other adjuvant therapy strategies to improve the prognosis of patients. Established a radiomics machine learning model based on multimodal MRI and clinical data, and analyzed the preoperative prediction value of this model for microvascular invasion (MVI) of hepatocellular carcinoma (HCC). The preoperative liver MRI data and clinical information of 130 HCC patients who were pathologically confirmed to be pathologically confirmed were retrospectively studied. These patients were divided into MVI-positive group (MVI+) and MVI-negative group (MVI-) based on postoperative pathology. After a series of dimensionality reduction analysis, six radiomic features were finally selected. Then, linear support vector machine (linear SVM), support vector machine with rbf kernel function (rbf-SVM), logistic regression (LR), Random forest (RF) and XGBoost (XGB) algorithms were used to establish the MVI prediction model for preoperative HCC patients. Then, rbf-SVM with the best predictive performance was selected to construct the radiomics score (R-score). Finally, we combined R-score and clinical-pathology-image independent predictors to establish a combined nomogram model and corresponding individual models. The predictive performance of individual models and combined nomogram was evaluated and compared by receiver operating characteristic curve (ROC). Alpha-fetoprotein concentration, peritumor enhancement, maximum tumor diameter, smooth tumor margins, tumor growth pattern, presence of intratumor hemorrhage, and RVI were independent predictors of MVI. Compared with individual models, the final combined nomogram model (AUC: 0.968, 95% CI: 0.920-1.000) constructed by radiometry score (R-score) combined with clinicopathological parameters and apparent imaging features showed the optimal predictive performance. This multi-parameter combined nomogram model had a good performance in predicting MVI of HCC, and had certain auxiliary value for the formulation of surgical plan and evaluation of prognosis.

ICG-Fluorescence Imaging for Margin Assessment During Minimally Invasive Colorectal Liver Metastasis Resection

Unintended tumor-positive resection margins occur frequently during minimally invasive surgery for colorectal liver metastases and potentially negatively influence oncologic outcomes. To assess whether indocyanine green (ICG)-fluorescence-guided surgery is associated with achieving a higher radical resection rate in minimally invasive colorectal liver metastasis surgery and to assess the accuracy of ICG fluorescence for predicting the resection margin status. The MIMIC (Minimally Invasive, Indocyanine-Guided Metastasectomy in Patients With Colorectal Liver Metastases) trial was designed as a prospective single-arm multicenter cohort study in 8 Dutch liver surgery centers. Patients were scheduled to undergo minimally invasive (laparoscopic or robot-assisted) resections of colorectal liver metastases between September 1, 2018, and June 30, 2021. All patients received a single intravenous bolus of 10 mg of ICG 24 hours prior to surgery. During surgery, ICG-fluorescence imaging was used as an adjunct to ultrasonography and regular laparoscopy to guide and assess the resection margin in real time. The ICG-fluorescence imaging was performed during and after liver parenchymal transection to enable real-time assessment of the tumor margin. Absence of ICG fluorescence was favorable both during transection and in the tumor bed directly after resection. The primary outcome measure was the radical (R0) resection rate, defined by the percentage of colorectal liver metastases resected with at least a 1 mm distance between the tumor and resection plane. Secondary outcomes were the accuracy of ICG fluorescence in detecting margin-positive (R1; <1 mm margin) resections and the change in surgical management. In total, 225 patients were enrolled, of whom 201 (116 [57.7%] male; median age, 65 [IQR, 57-72] years) with 316 histologically proven colorectal liver metastases were included in the final analysis. The overall R0 resection rate was 92.4%. Re-resection of ICG-fluorescent tissue in the resection cavity was associated with a 5.0% increase in the R0 percentage (from 87.4% to 92.4%; P < .001). The sensitivity and specificity for real-time resection margin assessment were 60% and 90%, respectively (area under the receiver operating characteristic curve, 0.751; 95% CI, 0.668-0.833), with a positive predictive value of 54% and a negative predictive value of 92%. After training and proctoring of the first procedures, participating centers that were new to the technique had a comparable false-positive rate for predicting R1 resections during the first 10 procedures (odds ratio, 1.36; 95% CI, 0.44-4.24). The ICG-fluorescence imaging was associated with changes in intraoperative surgical management in 56 (27.9%) of the patients. In this multicenter prospective cohort study, ICG-fluorescence imaging was associated with an increased rate of tumor margin-negative resection and changes in surgical management in more than one-quarter of the patients. The absence of ICG fluorescence during liver parenchymal transection predicted an R0 resection with 92% accuracy. These results suggest that use of ICG fluorescence may provide real-time feedback of the tumor margin and a higher rate of complete oncologic resection.

The role of free flap reconstruction after resection of extremity and trunk soft tissue sarcomas. Results of two referral centers in Argentina

IntroductionFor patients affected by extremity or trunk soft-tissue sarcomas (STS) large resections might be needed to achieve negative margins. This is a common scenario especially in locally advanced or recurrent tumors often within a pre-irradiated field. The objective of this study was to evaluate the results of free-flap reconstructions (FFR) after sarcoma surgery. ObjectiveThe endpoints were surgical results, quality of surgical margins and oncological outcome. MethodsRetrospective analysis of patients with extremity and trunk STS with free-flap reconstruction between 2008 and 2022. Demographic and tumor data, perioperative treatment, margin status, morbidity and evolution were evaluated. ResultsOf 467 patients, 25 (5.35%) required 26 free-flap reconstructions. Surgery was performed on an irradiated field in 8 (32%) patients. Reconstructions were mostly needed for distal lower extremity resections and the most common type of flap used was antero-lateral tight (ALT) flap. No R2 resections were performed. R0 and R1 resections were achieved in 22 (84.6%) and 4 (15.4%), respectively. All R1 resections were preplanned positive along a preserved critical structure. Surgical morbidity rate was 26% (7/26) and the re-operation rate was 15% (4/26) with 7.7% flap losses (2/26). At a median follow-up of 38 months, 7 (28%) patients presented local recurrences. ConclusionIn a referral sarcoma center, having a multidisciplinary surgical team capable of complex resections and reconstructions is of utmost importance for a correct and integral surgical planning. This allows optimal oncologic resections with acceptable morbidity.

Spatial distribution of tumor-resident macrophages as predictive biomarkers in endometrial cancer.

To investigate the role of CD47 expression and its relationship with tumor-resident macrophages, specifically at the tumor margin, in patients with type II endometrial cancer. This study aims to elucidate whether CD47 could serve as a prognostic marker and to understand the dynamics between CD47 and macrophages, which could inform new therapeutic strategies. A retrospective cohort study was conducted involving 75 patients of type II endometrial. Immunohistochemical analysis was performed to assess CD47 expression and macrophage markers (CD68 and CD163). The study found no direct correlation between CD47 expression levels and overall survival (p = 0.32), challenging its role as an independent prognostic marker in type II endometrial cancer. The higher expression of CD47 had significantly less incidence of endometrioid carcinoma G3 (p = 0.047). The negative correlation between CD47 H-score and the density of CD68-positive macrophages at tumor margin was statistically significant (p = 0.049). A high density of CD68-positive macrophages at the tumor margin but a low density of CD163-positive macrophages at the tumor margin were associated with poorer prognosis (p = 0.036). The complex interaction between CD47 and macrophages, particularly at the tumor margin, suggests new avenues for targeted therapy in type II endometrial cancer.

Abstract P64: Adipose-enriched Peri-tumoral Stroma Prognosticates Poorer Survival in Breast Cancers

Abstract Background: Breast cancers display a large degree of diversity between and within tumors. Intra-tumoral heterogeneity is contributed by variations in tumor cells and non-malignant stromal and immune cells of the tumor microenvironment (TME). So far, studies on the TME have focused on intra-tumoral stroma, whereas little attention has been given to the peri-tumoral microenvironment, extending beyond the tumor margins into the surrounding histologically normal-appearing tissues. Here, we hypothesized that intrinsic intra-tumoral heterogeneity impacts the more distal peri-tumoral stroma, which may in turn affect tumor growth and development. Methods: A systematic, multi-regional transcriptomic profiling analysis of the tumor and peri-tumoral regions from 8 ER+/PR+/HER2− invasive breast carcinomas was performed using the human Clariom™ S Assay. For each patient, 5 spatially distinct tumor samples were obtained, while peri-tumoral samples were collected from 4 different sides and at varying distances up to 7 cm from tumor margins. Pathway enrichment analyses and cellular deconvolution were performed to determine their molecular characteristics and cell type compositions. Gene expression signatures identified from peri-tumoral samples were applied to tumor-adjacent normal RNA-seq samples from 50 TCGA ER+/PR+/HER2− breast cancer patients to determine their prognostic value. Results: The 8 tumors displayed varying levels of spatial diversity in their biological properties, including 3 tumors with basal-classified regions. Four peri-tumoral clusters with distinct pathway activities and cell compositions were identified, but were independent of distance and location to the tumor. Two clusters reflect the major breast peri-tumoral states – a pro-inflammatory, adipose-enriched phenotype which was significantly associated with poorer overall survival (HR=4.28, p-value=0.02), and an adaptive immune cell- and myofibroblast-enriched phenotype. Conclusion: This suggests that the peri-tumoral stroma may be an important determinant in cancer progression. Moreover, independent of spatially-defined patterns, the peri-tumoral phenotype appears to be driven by inter-individual variations in the proportion of fibroglandular and fat tissue of the breast. Citation Format: Hannah Si Hui Lau, Veronique Kiak Mien Tan, Benita Kiat Tee Tan, Yirong Sim, Jelmar Quist, Aye Aye Thike, Puay Hoon Tan, Shazib Pervaiz, Anita Grigoriadis, Kanaga Sabapathy. Adipose-enriched Peri-tumoral Stroma Prognosticates Poorer Survival in Breast Cancers [abstract]. In: Proceedings of Frontiers in Cancer Science; 2023 Nov 6-8; Singapore. Philadelphia (PA): AACR; Cancer Res 2024;84(8_Suppl):Abstract nr P64.