Tumor Dimension Research Articles

Prevalence of Positive Level IIb Lymph Nodes in Tongue Carcinoma: Experience From a Tertiary Care Center in North India.

IntroductionComplications during and after dissection of level IIb lymph nodes include spinal accessory nerve (SAN) dysfunction, which results in the limitation of shoulder movements and, thus, hurts the quality of life. The current study aims to know the occurrence of level IIb lymph node positivity in tongue carcinoma.MethodsThis cross-sectional study was conducted from January 2019 to December 2019 in a tertiary care center in North India. Adult cases with primary ulcer-proliferative growth over the lateral border of the tongue were included in the study. The level IIb lymph node positivity from the postoperative histopathology report was the primary outcome measure of this study. To investigate the potential association of tumor size on level IIb lymph node positivity, we compared the maximum tumor dimensions among the level IIb lymph node-positive and -negative groups. In addition, to analyze the impact of the tumor's invasive nature on level IIb lymph node positivity, we compared the depth of invasion and proportion of cases with muscle involvement among the level IIb lymph node-positive and -negative groups. Lastly, to investigate their concurrent occurrences, we compared the number of level IIb lymph node-positive cases among the level IIa lymph node-positive and -negative groups.ResultsA total of 39 patients fulfilling the inclusion criteria were included in the study. Only six had positive level-IIb lymph nodes. No significant associations of tumor size, invasion depth, muscle invasion, or involvement of level IIa lymph nodes with the positivity of level IIb lymph nodes were found. However, only three were level IIb lymph node-positive in 28 level IIa lymph node-negative cases.ConclusionConsidering the low risk of isolated level IIb lymph node positivity in level IIa lymph node-negative cases, the dissection of level IIb nodes could be omitted during the surgical excision of the tumor. However, radiological investigations detecting metabolic activity should be used in the preoperative period and postoperative follow-up to detect early lymph node involvement and disease recurrence.

Clinicopathological factors influencing the number of stages of Mohs surgery for basal cell carcinoma

BackgroundMohs Micrographic Surgery (MMS) is commonly used to treat high-risk basal cell carcinoma (BCC). ObjectivesCorrelate clinicopathologic preoperative features with the number of MMS stages (primary endpoint) and margins (secondary endpoint) required for BCC complete excision. MethodsWe retrospectively analyzed BCCs treated by MMS in a 2-year period at the study’s institution. Variables studied included the patient gender, age, immune status, lesion size, location, if it was a primary, recurrent, or persistent tumor, histopathologic characteristics, number of surgical stages, and amount of tissue excised. Results116 BCCs were included. The majority (61.2%, n = 71) required a single-stage surgery for complete clearance, requiring a final margins of 3.11 ± 2.35 mm. Statistically significant differences between locations in different high-risk areas (periocular, perioral, nose, ear) and the number of MMS stages required for complete excision (p = 0.025) were found, with periocular tumours requiring the highest mean of stages (2.29 ± 0.95). An aggressive histopathology significantly influenced the number of MMS stages (p = 0.012). Any significant relation between clinicopathological features and variation in the final surgical margins was found, just certain tendencies (male patients, persistent tumor, periocular location, and high-risk histopathological tumors required larger margins). Neither patient age or tumor dimension correlated significantly with both number of MMS stages and final surgical margins. Study limitationsLimitations of this study include its single-center nature with a small sample size, which limits the value of conclusions. ConclusionMain factors related to a greater number of MMS stages were periocular location and high-risk histopathological subtype of the tumor.

Predicting surgical decision-making in vestibular schwannoma using tree-based machine learning.

Vestibular schwannomas (VSs) are the most common neoplasm of the cerebellopontine angle in adults. Though these lesions are generally slow growing, their growth patterns and associated symptoms can be unpredictable, which may complicate the decision to pursue conservative management versus active intervention. Additionally, surgical decision-making can be controversial because of limited high-quality evidence and multiple quality-of-life considerations. Machine learning (ML) is a powerful tool that utilizes data sets to essentialize multidimensional clinical processes. In this study, the authors trained multiple tree-based ML algorithms to predict the decision for active treatment versus MRI surveillance of VS in a single institutional cohort. In doing so, they sought to assess which preoperative variables carried the most weight in driving the decision for intervention and could be used to guide future surgical decision-making through an evidence-based approach. The authors reviewed the records of patients who had undergone evaluation by neurosurgery and otolaryngology with subsequent active treatment (resection or radiation) for unilateral VS in the period from 2009 to 2021, as well as those of patients who had been evaluated for VS and were managed conservatively throughout 2021. Clinical presentation, radiographic data, and management plans were abstracted from each patient record from the time of first evaluation until the last follow-up or surgery. Each encounter with the patient was treated as an instance involving a management decision that depended on demographics, symptoms, and tumor profile. Decision tree and random forest classifiers were trained and tested to predict the decision for treatment versus imaging surveillance on the basis of unseen data using an 80/20 pseudorandom split. Predictor variables were tuned to maximize performance based on lowest Gini impurity indices. Model performance was optimized using fivefold cross-validation. One hundred twenty-four patients with 198 rendered decisions concerning management were included in the study. In the decision tree analysis, only a maximum tumor dimension threshold of 1.6 cm and progressive symptoms were required to predict the decision for treatment with 85% accuracy. Optimizing maximum dimension thresholds and including age at presentation boosted accuracy to 88%. Random forest analysis (n = 500 trees) predicted the decision for treatment with 80% accuracy. Factors with the highest variable importance based on multiple measures of importance, including mean minimal conditional depth and largest Gini impurity reduction, were maximum tumor dimension, age at presentation, Koos grade, and progressive symptoms at presentation. Tree-based ML was used to predict which factors drive the decision for active treatment of VS with 80%-88% accuracy. The most important factors were maximum tumor dimension, age at presentation, Koos grade, and progressive symptoms. These results can assist in surgical decision-making and patient counseling. They also demonstrate the power of ML algorithms in extracting useful insights from limited data sets.

Photon-based High-dose Single-fraction Radiosurgery, an Effective Treatment Modality for Large and Posterior Uveal Melanoma.

Uveal melanoma (UM) is the most common primary intraocular malignant tumor. This malignancy is frequently treated using brachytherapy, stereotactic radiotherapy, or proton therapy. The objective of this study was to assess the role of stereotactic radiosurgery in the treatment of large and posterior UM. From January 2014 to July 2021, we treated 65 patients (median age=71 years; range=31-89 years) affected by UM. Inclusion criteria were Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤2, life expectancy >6 months, tumor thickness >10 mm, diameter >16 mm or posterior UM. The treatment was delivered with a True Beam™ LINAC with arc modulation technique. All patients received 27 Gy in one fraction (biological effective dose ≈100 Gy, assuming an α/β of 10). The median follow-up was 36 (range=3-90) months. Acute toxicities were reported in 14 patients, whereas late toxicity occurred in 45 (69.2%). Fifteen patients (23.0%) underwent enucleation: eight (12.3%) for failure of local control and seven (10.7%) for late treatment co-morbidities. The 5-year local control, and progression-free, metastasis-free, enucleation-free, and overall survival rates were 80%, 43%, 62%, 65% and 56%, respectively. In multivariate analysis, tumor dimensions significantly influenced survival [larger basal diameter: progression-free [hazard ratio (HR)=2.42] and overall (HR=2.61) survival; greater thickness: overall survival (HR=2.36)]. In multivariate analysis, patients without local control had a higher risk of distant metastasis (HR=3.25). Stereotactic radiosurgery offers an effective and safe approach for selected cases of UM due to the satisfactory results in terms of local control, eye conservation and survival.

The immunohistochemical molecular risk classification in endometrial cancer: A pragmatic and high-reproducibility method

IntroductionThe aim of this study is to assess the clinical reproducibility and the potential oncological validity of the molecular information provided by the immunohistochemistry (IHC) to properly stratify the endometrial cancer patients. MethodsRetrospective IHC analyses were conducted in a large series of 778 pre-operative uterine-confined ECs, studying the presence/absence of MLH1, MSH2, MSH6 and PMS2 to define the mismatch repair (MMR) stable or instable phenotype; the presence of p53 mutations and other molecular features. The molecular profile was correlated with histological, clinical and prognostic data. ResultsBased on IHC assessment, we defined 3 EC populations: stable MMR patients (MMRs), instable patients (MMRi) and p53 mutated patients (p53+). Our result demonstrated that the IHC stratification statistically correlated with the most relevant pathologic-clinical features: FIGO stage (p < 0.001), grading (p < 0.001), histotype (p < 0.001), presence of LVSI (p < 0.001), myometrial invasion and tumor dimension (p = 0.003 for both). These 3 IHC populations statistically reflected the EC risk class ESGO-ESMO-ESP classification 2021 (p < 0.001). These results were also confirmed in the Kaplan-Meier curves in terms of overall survival (OS) and disease-free survival (DFS) (p < 0.0001). The multivariate analyses demonstrated that absence of estrogen receptor (ER) impacted the OS (p = 0.011) and, the Age > 60 years and the ER-status the DFS (p = 0.041 and p = 0.004). ConclusionIn this large series, we demonstrated that the pragmatic and systematic use of IHC may have an important role to properly stratify, in terms of histological features and clinical outcomes, the EC patients.

Subgingival Periopathogens Assessment and Clinical Periodontal Evaluation of Gastric Cancer Patients—A Cross Sectional Pilot Study

Oral microbiota have shown a higher bacterial diversity in patients with cancers of the digestive tract, with higher levels of periopathogens. Recent studies have shown that Fusobacterium links to gastro-intestinal neoplastic tissue and accelerates its progression, as well as worsening patient outcome. The present pilot study was carried out between February and December 2020 to evaluate the possible association between the abundance of some periopathogens (Fusobacterium nucleatum, Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Treponema denticola and Tannerella forsythia) in subgingival plaque and periodontal status with characteristics of gastric cancer. The study was performed on a sample of 24 patients with gastric cancer from the 1st Department of Surgery and Department of Gastroenterology within the Clinical County Hospital of Emergency of Craiova, Romania. The patients’ oral cavity was examined, gingival crevicular samples were collected, and signs of periodontal disease were recorded. On the histopathological exam, the differentiation grade and size of the tumour were registered. Our results showed that, from the periopathogens studied, the most abundant bacteria were F. nucleatum followed by T. forsythia in all groups. In our present study, the strong correlation between tumour dimension and all periodontal parameters but also between tumour dimension and F. nucleatum could suggest a positive association between periodontal disease, tumoral growth and periopathogens implication in this process.

Automated Koos Classification of Vestibular Schwannoma.

The Koos grading scale is a frequently used classification system for vestibular schwannoma (VS) that accounts for extrameatal tumor dimension and compression of the brain stem. We propose an artificial intelligence (AI) pipeline to fully automate the segmentation and Koos classification of VS from MRI to improve clinical workflow and facilitate patient management. We propose a method for Koos classification that does not only rely on available images but also on automatically generated segmentations. Artificial neural networks were trained and tested based on manual tumor segmentations and ground truth Koos grades of contrast-enhanced T1-weighted (ceT1) and high-resolution T2-weighted (hrT2) MR images from subjects with a single sporadic VS, acquired on a single scanner and with a standardized protocol. The first stage of the pipeline comprises a convolutional neural network (CNN) which can segment the VS and 7 adjacent structures. For the second stage, we propose two complementary approaches that are combined in an ensemble. The first approach applies a second CNN to the segmentation output to predict the Koos grade, the other approach extracts handcrafted features which are passed to a Random Forest classifier. The pipeline results were compared to those achieved by two neurosurgeons. Eligible patients (n = 308) were pseudo-randomly split into 5 groups to evaluate the model performance with 5-fold cross-validation. The weighted macro-averaged mean absolute error (MA-MAE), weighted macro-averaged F1 score (F1), and accuracy score of the ensemble model were assessed on the testing sets as follows: MA-MAE = 0.11 ± 0.05, F1 = 89.3 ± 3.0%, accuracy = 89.3 ± 2.9%, which was comparable to the average performance of two neurosurgeons: MA-MAE = 0.11 ± 0.08, F1 = 89.1 ± 5.2, accuracy = 88.6 ± 5.8%. Inter-rater reliability was assessed by calculating Fleiss' generalized kappa (k = 0.68) based on all 308 cases, and intra-rater reliabilities of annotator 1 (k = 0.95) and annotator 2 (k = 0.82) were calculated according to the weighted kappa metric with quadratic (Fleiss-Cohen) weights based on 15 randomly selected cases. We developed the first AI framework to automatically classify VS according to the Koos scale. The excellent results show that the accuracy of the framework is comparable to that of neurosurgeons and may therefore facilitate management of patients with VS. The models, code, and ground truth Koos grades for a subset of publicly available images (n = 188) will be released upon publication.

The role of imaging in diagnosis and management of malignant peritoneal mesothelioma: a systematic review.

Imaging of the peritoneum and related pathology is a challenge. Among peritoneal diseases, malignant peritoneal mesothelioma (MPeM) is an uncommon tumor with poor prognosis. To date, there are no specific guidelines or imaging protocols dedicated for the peritoneum and MPeM. The objective of this study was to analyze the literature describing imaging modalities used for MPeM to determine their relative clinical efficacy and review commonly reported imaging features of MPeM to promote standardized reporting. We performed a systematic review of original research articles discussing imaging modalities in MPeM from 1999 to 2020. Effectiveness measures and common findings were compared across imaging modalities. Among 582 studies analyzed, the most-used imaging modality was CT (54.3%). In the differentiation of MPeM from peritoneal carcinomatosis, one study found CT had a diagnostic sensitivity of 53%, specificity of 100%, and accuracy of 68%. Two studies found fluorodeoxyglucose positron emission tomography (FDG-PET) had sensitivity of 86-92%, specificity of 83-89%, and accuracy of 87-89%. Another study found magnetic resonance imaging (MRI) was the best predictor of the peritoneal carcinomatosis index. Characteristics shown to best differentiate MPeM from other diseases included ascites, peritoneal thickening, mesenteric thickening, pleural plaques, maximum tumor dimension, and number of masses. Most published MPeM imaging studies utilized CT. PET/CT or MRI appear promising, and future studies should compare effectiveness of these modalities. MPeM imaging reports should highlight ascites, number of and maximum tumor dimension, peritoneal/mesenteric thickening, and associated pleural plaques, allowing for better aggregation of MPeM imaging data across studies.

Comparison of excised breast volume, re-excision rate and margin positivity in breast-conserving surgery in breast cancer patients using and not using neoadjuvant chemotherapy

Background/Aim: One of the purposes of using neoadjuvant chemotherapy (NAC) is to evaluate the patients according to tumor-to-gland ratio, save them from mastectomy by reducing tumor dimension, and get more beautiful results cosmetically with less volume excision during breast-conserving surgery (BCS). Is it possible to achieve the goal of less volume excision after NAC? We aimed to compare the excised volume with BCS, margin positiveness and re-excision rates between the patients who received NAC and the ones who didn’t receive NAC in patients with breast cancer and to calculate the increase in BCS performability with NAC. Methods: Among 306 patients diagnosed with breast cancer between 2013 and 2021 at Gaziosmanpasa Training and Research Hospital, 105 patients who underwent BCS were included in this retrospective cohort study. Excised breast volume, surgical margin positiveness, re-excision and mastectomy rates were retrospectively compared in breast cancer patients underwent BCS with and without NAC. The patients who received BCS following NAC were named the primary chemotherapy (PC), and the patients whose treatment was initiated with BCS were named the primary surgery (PS) groups. Results: BCS was performed to 105 breast cancer patients, of which 28 (26.7%) received NAC, and 77(73.7%) started the treatment with surgery. There were no significant differences between the PC and PS groups with respect to excision volume (755.86 (725.69) and 709 (637.36), P=0.822). Re-excision was more common in PS than in the PC group (39.0% vs 10.7%, P=0.008). Fourteen patients who were candidates for mastectomy at the beginning, became eligible for BCS by receiving NAC, which caused a 15.38% increase in BCS applicability. Surgical margin positivity was seen in only 3 patients, which is why a statistical comparison wasn’t made. Conclusions: Although the tumor size was higher in the PC group, the excised breast volume did not show a significant difference between the two groups. PC decreased the re-excision rates in the chemotherapy candidate group. This data shows that patients who are candidates for adjuvant chemotherapy might be considered for PC to increase BCS success with lower re-excision rates and equivalent excised breast volume.

Impact of neoadjuvant immune checkpoint inhibitor therapy on primary tumor size and complexity: Correlation with surgical quality and short term oncological outcomes.

390 Background:The concept of primary systemic therapy has gained increasing traction in the management of metastatic and locally advanced Renal Cell Carcinoma (RCC). Most series have evaluated the use of tyrosine-kinase inhibitors, however, with the emergence of immune checkpoint inhibitor therapy as first line agents in advanced RCC, further assessment of efficacy is warranted. We examined the effects of immunotherapy (IO) combinations on the primary tumor and consequent surgical quality and short-term oncological outcomes. Methods: We conducted a multi-center, retrospective analysis of patients with advanced/metastatic RCC having received IO followed by Radical (RN) or partial nephrectomy (PN). Primary outcome was achievement of Bifecta (composite outcome of complete resection and no 30-day post-operative complications). Predictors for achievement of Bifecta were assessed with logistic regression multivariable analysis. Secondary outcomes were change in maximal tumor dimension, RENAL nephrometry score and disease progression. Kaplan-Meier analysis was used to assess progression-free survival (PFS) for Bifecta and non-Bifecta patients. Results: We identified 52 patients with advanced RCC across 9 institutions who were eligible. The median age was 63 years and 60.4% were males. Median tumor size at diagnosis was 9.3 cm. 19.6% had T4 disease and 75% had AJCC Stage IV disease. IO treatment resulted in significant reductions in median tumor size (-25.4%; 9.7 cm vs. 7.3cm p = 0.0129) and RENAL nephrometry score (9 to 8, p = 0.032). 43 (83%) of patients underwent RN and (9) 17% had PN. Median tumor size was smaller for PN (8 vs. 4.1 cm, p &lt; 0.001), and 30 day complication rates were higher (p = 0.024). Bifecta was achieved in 39 patients [33/42 (78.6%) RN and 6/9 (67%) PN, p = 0.264). Predictors for achievement of Bifecta were younger age (OR 1.06, p = 0.01), increasing reduction in tumor size (OR 1.187, p &lt; 0.001), and shorter time between therapy and surgery (OR 1.07, p &lt; 0.001). Kaplan-Meier analysis demonstrated longer median time to progression in the Bifecta-positive group compared to patients who failed to achieve Bifecta (75 vs. 30 months, p = 0.04). Conclusions: Pre-surgical therapy resulted in tumor size and complexity reduction. Tumor size reduction was predictive for achievement of Bifecta, which was associated with improved short term oncological outcomes. To our knowledge, this is the first series evaluating the effect of neoadjuvant systemic therapy on the primary tumor prior to surgical intervention.

Radiomic Analysis of Tumour Heterogeneity Using MRI in Head and Neck Cancer Following Chemoradiotherapy: A Feasibility Study.

ObjectivesTo evaluate interval changes in heterogeneity on diffusion-weighted apparent diffusion coefficient (ADC) maps and T1-weighted post-gadolinium (T1w post gad) MRI in head and neck carcinoma (HNSCC), with and without chemo-radiotherapy (CRT) response.MethodsThis prospective observational cohort study included 24 participants (20 men, age 62.9 ± 8.8 years) with stage III and IV HNSCC. The primary tumour (n = 23) and largest lymph node (n = 22) dimensions, histogram parameters and grey-level co-occurrence matrix (GLCM) parameters were measured on ADC maps and T1w post gad sequences, performed pretreatment and 6 and 12 weeks post CRT. The 2-year treatment response at primary and nodal sites was recorded. The Wilcoxon signed-rank test was used to compare interval changes in parameters after stratifying for treatment response and failure (p < 0.001 statistical significance).Results23/23 primary tumours and 18/22 nodes responded to CRT at 2 years. Responding HNSCC demonstrated a significant interval change in ADC histogram parameters (kurtosis, coefficient of variation, entropy, energy for primary tumour; kurtosis for nodes) and T1w post gad GLCM (entropy and contrast in the primary tumour and nodes) by 6 weeks post CRT (p < 0.001). Lymph nodes with treatment failure did not demonstrate an interval alteration in heterogeneity parameters.ConclusionsADC maps and T1w post gad MRI demonstrate the evolution of heterogeneity parameters in successfully treated HNSCC by 6 weeks post CRT; however, this is not observed in lymph nodes failing treatment.Advances in KnowledgeEarly reduction in heterogeneity is demonstrated on MRI when HNSCC responds to CRT.

Abstract P5-13-34: A multi-modal biomarker of immunotherapy response

Abstract Background Immunotherapy (IO) is expected to become a part of standard neoadjuvant therapy for early-stage, triple-negative breast cancer. However, only a minority of patients benefit from the addition of IO to standard neoadjuvant chemotherapy (NACT). Biomarkers of IO response in the metastatic setting, such as PD-L1 expression, fail to predict benefit from IO in the early-stage setting. Given the financial cost of IO and the potential for irreversible, immune-related toxicities, predictive biomarkers are desperately needed. SimBioSys TumorScope (TS), a commercially available biophysical model, has been previously validated as a highly accurate predictor of response to standard NAT regimens. TS has the potential to identify patients treated with IO who would have responded well to standard NACT, and those who truly benefited from IO, enabling biomarker discovery. Methods We identified 17 pts who received pembrolizumab in combination with standard NACT. From these cases, dynamic contrast-enhanced MRIs were assessed from multiple timepoints throughout treatment. Using a proprietary convolutional neural net, the tumor region from each MRI was segmented to assess volume over time. We compared actual tumor volumes to predicted response to standard NACT (without pembrolizumab) generated with the TS platform. By contrasting the tumor volume across the simulation and the longitudinal MRI timepoints, a metric of response directly attributable to pembrolizumab (“IO benefit”) was generated. Clinical, radiological, metabolic, tumor morphology, and microvasculature features were extracted from TS simulations, and after quality control and removal of redundant metrics, used in linear models as predictors of IO benefit. Results Nine clinical, seven metabolic, 16 microvasculature, ten tumor morphology, and 77 radiological features were used as individual predictors of IO benefit in linear models. Eight out of 17 cases had positive IO benefit values. In all, 12 out of the 119 metrics of interest nominally significant predictors of IO benefit (p&amp;lt;0.05). Top relationships of interest included: tumor convex hull surface area to volume ratio (b=-51.4, p=0.010), maximum 2D diameter column (a metric of longest tumor dimension) (b=1.8, p=0.011), and percentage of tumor cells with low oxygen concentration at simulation outset (hypoxic fraction) (b=1.0, p=0.034). In further analyses, we observed nominally significant relationships between IO benefit and hypoxic fraction measures taken across simulation timepoints. Significant relationships were salient in hypoxic fraction measures taken at early simulation timepoints, including weeks three (p=0.017), two (p=0.024), and five (p=0.038). Importantly, between IO benefit/hypoxic fraction relationships, we observed concordant positive directions of effect (i.e., higher hypoxic cancer fraction, higher IO benefit). Conclusion IO is likely to soon gain regulatory approval for early-stage TNBC, but biomarkers to predict benefit are lacking. PD-L1 expression has previously been correlated with hypoxic tumor environments and high density of tumor infiltrating lymphocytes. Even within a limited dataset, TS provided a biologically explainable marker to identify patients who may benefit from IO. Work is underway to further validate these findings in a larger dataset, and to validate hypoxic tumor fraction as a predictor of IO response. Citation Format: JR Pfeiffer, Joseph R. Peterson, Frederick Howard, Tyler M. Earnest, Tushar Pandey, Gong He, Rita Nanda. A multi-modal biomarker of immunotherapy response [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P5-13-34.

Abstract P3-18-16: Breast conserving surgery in BRCA-mutation carriers. A single Institution experience

Abstract BackgroundBRCA-mutation carriers have a lifetime risk of breast cancer (BC) that ranges from 36 to 70%. For patients (pts) without mutation, breast conserving surgery (BCS) (followed by radiation therapy) is the treatment of choice since it offers similar survival to that of unilateral mastectomy. However, the optimal local management in BRCA-mutation carriers remains a matter of debate and the role of bilateral salpingo-oophorectomy (BSO) in reducing BC risk might be influenced by age and medical BC treatments (such as GnRH analogues). Patients and methodsWe retrieved clinical pathologic characteristics of 124 BRCA-mutated BC pts, consecutively tested at our Institution from 2008 to 2018. Primary end-point was recurrence-free survival (RFS) evaluation in terms of disease-free survival (DFS), distant DFS (DDFS) and overall survival (OS). Secondary end-point was identification of independent predictive factors for BCS. Clinical pathologic characteristics were evaluated and compared using univariate and multivariate analysis. Kaplan-Mayer curves were used to describe DFS, DDFS and OS. ResultsMedian age at BC surgery was 41 years (range 24-74), most of the pts (79%) were pre-menopausal and presented with ductal invasive carcinoma (91.9%). As per biological subtype, 63 (50.8%) pts had luminal-like BC, 52 (41.9%) triple negative (TN) BC and 9 (7.3%) HER2 enriched-like BC. More than half pts (62.9%) presented with G3 tumors and median Ki-67 was 40% (range 5-95). 17 (13.7%) and 80 (64.5%) pts underwent neo-adjuvant and adjuvant chemotherapy, respectively; 64 (51.6%) pts received adjuvant endocrine therapy, 39 (31.5%) with the addition of GnRH analogue. When comparing BCS to mastectomy, regardless of BSO, we could not observe any statistically significant difference in all the RFS end-points. 10-year DFS rate was 56.4% and 79.5%, respectively (p=0.187); 10-year DDFS rate was 83.7% and 82.3%, respectively (p=0.689); 10-year OS rate was 87.7% and 85.1%, respectively (p=0.947). At a multivariate analysis, age ≤41 years (p=0.008; OR 0.309; 95% CI 0.190-0.513) and primary tumor dimension ≤21 mm (p=0.008; OR 0.320; 95% CI 0.114-0.426), were the only predictors of breast surgery type (BCS compared to any other surgical treatment). ConclusionsOur data suggest that young pre-menopausal BRCA-mutated pts with small tumors may not need up-front mastectomy and BSO might be postponed, when ovarian cancer risk epidemiologically rises and potential reproductive desire is fulfilled. Citation Format: Agnese Losurdo, Damiano Gentile, Monica Zuradelli, Andrea Sagona, Erika Barbieri, Monica Barile, Paolo Bianchi, Rosalba Torrisi, Wolfgang Gatzemeier, Marta Scorsetti, Corrado Tinterri, Armando Santoro. Breast conserving surgery in BRCA-mutation carriers. A single Institution experience [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-18-16.

Analysis of Clinical Outcomes of Patients with Soft Tissue Sarcoma.

The aim of this study was to evaluate the outcome of patients with soft tissue sarcoma of the extremity and abdominal wall. This is the retrospective analysis of patients from a prospectively maintained data base from a single institute. We identified 79 patients with intermediate- to high-grade soft tissue sarcomas who were treated at our institute between Jan 2015 and July 2018. Low-grade tumors were excluded. There were 60 males and 19 females with a mean age of 44.6years. Of the 79 sarcomas, 50 were in the lower limb and 24 in the upper limb and 5 were in abdominal wall. The commonest subtypes were undifferentiated pleomorphic sarcoma (n = 21) and synovial sarcoma (n = 19). Only 9 patients had metastatic disease at presentation. All 79 patients underwent surgical resection with an intent to achieve clear margins. Amputation was done in 19 patients while wide excision of the tumor was done in 60 patients. Adjuvant radiotherapy was given in 49 patients while adjuvant chemotherapy was given in 35 patients. At last follow-up (73 patients), 48 patients are alive without disease, 9 are alive with disease, 12 patients had died of disease, and 4 patients died due to other causes. Overall survival(OS) for 3year is 77.6%, and estimated mean survival is 55.05months. Relapse-free surviva(RFS)l at 3year is 74.3%, and estimated mean RFS is 51.78. The only independent factor that affected the OS was the dimension of primary tumor (p = 0.02). For disease-free survival, the independent factors that affected outcome were stage at presentation (p = 0.04) and dimension of the tumor (p = 0.04). Short-term results shown by this study shows good outcome in patient with intermediate- to high-grade sarcomas when multidisciplinary approach is utilized for the management. Patients who had metastatic disease at presentation did worse than patients who did not.

Evaluating the therapeutic effect of tumor treating fields (TTFields) by monitoring the impedance across TTFields electrode arrays.

BackgroundTumor Treating Fields (TTFields), are a novel, non-invasive tissue ablation technology for treatment of cancer. Tissue ablation is achieved through the continuous delivery of a narrow range of electromagnetic fields across a tumor, for a period of months. TTFields are designed to affect only cells that divide and to interfere with the cell division process. The therapy is monitored with MRI imaging, performed every couple of months. Current technology is unable to assess the treatment effectiveness in real time.MethodsWe propose that the effect of the treatment can be assessed, in real time, by continuously measuring the change in electrical impedance across the TTFields delivery electrode arrays. An in vitro anatomic skull experimental study, with brain and tumor mimics phantom tissues was conducted to confirm the potential value of the proposed monitoring system.ResultsExperiments show that measuring the change in the impedance amplitude between opposite TTFields electrode arrays, at a typical TTFields treatment frequency of (200 kHz), can detect changes in the tumor radius with a sensitivity that increases with the radius of the tumor. The study shows that TTFields electrode arrays can be used to assess the effectiveness of TTFields treatment on changes in the tumor dimensions in real time, throughout the treatement. This monitoring system may become a valuable addition to the TTFields cancer treatment technology. It could provide the means to continuously assess the effectiveness of the treatment, and thereby optimize the design of the treatment protocol.

Combined Positive Score for Programmed Death Ligand-1 Expression and Inflammatory Microenvironment in Gastrointestinal Stromal Tumors.

Background and Objectives: GISTs are the most frequent type of mesenchymal neoplasm of the digestive tract. The prognosis is mainly determined by tumor dimensions, mitotic rate and location, but other less well-documented factors can influence evolution and survival. The immune microenvironment and checkpoint molecule expression were proven to impact the prognosis in different types of cancer. The aim of this study was to determine PD-L1 expression in GISTs and to evaluate the level of intratumoral immune infiltration in relation to prognostic variables and survival. Materials and Methods: Sixty-five GISTs diagnosed in the same institution between 2015 and 2018 were immunohistochemically tested for PD-L1 and evaluated using CPS. Immune cells were emphasized, with CD3, CD4, CD8, CD20 and CD68 antibodies and quantified. All data were processed using statistical tools. Results: The median age was 61 years (range, 28–78) and 36 patients (55.4%) were males. The location of the tumors was predominantly gastric (46%), followed by the small bowel (17%) and colorectal (6%). In addition, 11% were EGISTs and 20% were secondary tumors (11% metastases and 9% local recurrences). PD-L1 had a variable expression in tumor and inflammatory cells, with a CPS ranging from 0 to 100. Moreover, 64.6% of cases were PD-L1 positive with no significant differences among categories of variables, such as the age and the sex of the patient, tumor location, the primary or secondary character of the tumor, dimensions, mitotic rate, the risk of disease progression and tumor cell type. Immune cells had a variable distribution throughout the tumors. CD3+ lymphocytes were the most frequent type. CD20+ cells were identified in a larger number in tumors ≤5 cm (p = 0.038). PD-L1-positive tumors had a higher number of immune cells, particularly CD3+, CD20+ and CD68+, in comparison to PD-L1-negative ones (p = 0.032, p = 0.051, p = 0.008). Epithelioid and mixed cell-type tumors had a higher number of CD68+ cells. Survival was not influenced by PD-L1 expression; instead, it was decreased in multifocal tumors (p = 0.0001) and in cases with Ki67 ≥ 50% (p = 0.008). Conclusions: PD-L1-positive expression and the presence of different immune cell types, in variable quantities, can contribute to a better understanding of the complex interactions between tumor cells and the microenvironment, with a possible therapeutic role in GISTs.

Complications of transanal endoscopic resection in cancer recti

Objective. To study іntra- and postoperative complications in transanal endoscopic resection in patients, suffering cancer recti and to reduce this quantity.&#x0D; Materials and methods. Through the period 2009 - 2021 yrs on the base of Odessa Regional Clinical Hospital 184 patients, suffering cancer recti, were operated, using transanal endoscopic resection. The patients’ age was from 42 to 86 yrs old. The patients were distributed into two groups. In 90 patients of the first group the cancer recti diagnosis of stage I (T1-2N0M0) was established. In 94 patients of the second group the diagnosis of cancer recti stage ІІ (T3N0M0) was established.&#x0D; Results. Purulent-septic, thromboembolic and urological complications were absent in all 184 patients, as well as severe intraoperative complications and mortality. The average stationary stay of the patients have constitited (3.4 ± 1.7) days (from 2 to 6 days). The average lower edge of the tumour was situated at a distance (9.5 ± 4.2) cm (from 5 to 16 cm) from the anal channell, and the average dimensions of tumour - (2.8 ± 1.7) cm (from 1.5 to 4 cm). While studying of the histological investigations results there was noted, that in all the patients the tumour was excised in the healthy tissues borders in accordance to oncological technique. Period of follow-up have constituted from 12 to 60 mo. Cancer recti recurrence was revealed in 12 (13.3%) patients of the first group. Cancer recurrence have had occur in patients, who have rejected from conduction of chemo- and radiotherapy. The patients with recurrences were reoperated, using classic low anterior rectal resection with total mesorectumectomy.&#x0D; Conclusion. While conduction of preoperative neoadjuvant chemo- and radiotherapy the tumour dimensions are reduced significantly, as well as quantity of іntra- and postoperative complications in performance of transanal endoscopic resection. The disease prognosis for cancer recti depends directly on presence of metastases in regional «sentinel» lymphatic nodes.

Radiological work‐up for proton beam therapy of uveal melanoma patients

AbstractPurposeIn ocular proton beam therapy (PBT), 2.5 mm tantalum clips are surgically sutured near the tumour border for clinical target volume marking. The clip‐tumour distances are assessed peroperative using transillumination, indentation and or fundoscopy. To support the clip localisation, target definition and 3D tumour modelling, a dedicated MRI‐protocol was developed and evaluated.Methods23 consecutive uveal melanoma (UM) patients, planned for PBT, were scanned on a 3T MRI. MRI based clip‐tumour distances were compared with the peroperative measurements. For clips with more than 1mm difference, the most likely origin of this discrepancy was discussed in a multidisciplinary setting.ResultsIn 39/87 (45%) of the clips, both measurements differed more than 1 mm. For the majority of these clips, the MRI showed a larger clip‐tumour distance (n = 30). Largest differences were observed in flat UM (n = 13) where an average absolute difference of 3.9 mm was found. Here, MRI was generally considered less reliable as the extend of flat tumours is difficult to determine on MRI. In 15% of the clips, the discrepancy was attributed to a complex tumour geometry. Here an average absolute difference of 3.2 mm was observed. In these cases 3D imaging provided valuable additional information for the treatment planning. In 10% of the clips, the anterior localized tumour casted a shadow, resulting in an overestimation of the tumour dimensions during surgery, leading to an average absolute difference of 3.7 mm. For these patients, MR‐imaging was considered more reliable as obtaining correct peroperative measurements was difficult.ConclusionsMRI and peroperative measurements were equal in 55% of the cases. For flat UM, MRI generally underestimates tumour dimensions. For complex and anterior UM, MRI‐based clip‐tumour measurements are more reliable, which could result in more accurate target definition, thereby possibly reducing toxicity and improving probability to retain vision.

Macroscopic Examination of Surgical Specimen of Papillary Thyroid Carcinoma.

Standardized pathology reporting of thyroid cancer is important for quality clinical management, research as well as education purposes. International Collaboration on Cancer Reporting (ICCR) has produced a Dataset for reporting carcinoma of thyroid. Of the 19 core elements to report, six (operative procedure, operative findings, specimen submitted, tumor focality, tumor site, tumor dimensions) depend on the proper macroscopic examination of the surgical specimen with thyroid carcinoma. The other core elements to report depend on proper and adequate sampling on macroscopic examination. Thus, proper handling, examination, dissection, and sampling of different types, the surgical specimen(s) are needed in different situations for patients with thyroid carcinomas.

Surgical treatment of glial tumors of the paralimbic system

Tumors of the paralimbic system were considered inoperable for a long time due to high risk of postoperative complications. However, there have been significant changes in surgical tactics for these neoplasms over the past decades. Despite the improvement of surgical principles for these tumors and development of new approaches, risks of surgical treatment are still high (up to 33.6%). To assess the results of surgical treatment of paralimbic glial tumors and identify predictors of adverse outcomes. We retrospectively analyzed postoperative outcomes in 52 patients with paralimbic glial tumors at the neurosurgical department of the Pirogov National Medical Surgical Center between 2016 and 2020. Tumor dimensions and topography with surrounding structures were evaluated using preoperative MRI. Resection quality was evaluated within the first postoperative day considering MRI data. We applied transcranial or transcortical electrostimulation, direct cortical and subcortical bi- and monopolar stimulation for intraoperative functional assessment of corticospinal tract. Neurological examination was performed prior to surgery, after 24 hours, 7 days, and 6 months. Total resection was performed in 39 patients, almost total - 5 patients, subtotal - 6 patients, partial resection - 2 patients. Mean volume of tumors before surgery was 95.1±55.1 cm3. After surgery, volume ranged from 0 to 24.7 cm3 (mean 2.2±5.01 cm3). After 24 hours, neurological symptoms de novo or aggravation of preoperative motor deficit was revealed in 17 (33%) patients. However, this impairment regressed in most patients, and only 4 (7%) patients retained these disorders after 6 months. Transcortical or combined surgical approach in conjunction with multimodal neurophysiological monitoring allows total or close to total resection of paralimbic glioma in 85% of cases. Risk of postoperative complications is 7%. Unfavorable prognostic factors of neurological impairment are decrease in muscle response amplitude ≥50% according to transcranial neurophysiological stimulation and tumor spread medial to perforator arteries.