Tumor budding (TB) in Colorectal Cancer (CRC), The Best Slide To Count On!

Abstract Introduction/Objective TB is a strong prognosticator in CRC. The international TB consensus conference (ITBCC, 2016) proposed a “hot spot” approach for TB grading. We aimed to identify the characteristics of sections with the highest TB grade utilizing ITBCC’s method. Methods Resected CRC cases, excluding treated cases, were retrieved. All tumor sections were examined. Section TB grade(sTB) was noted. The highest sTB was deemed the final TB grade(fTB) of each case. The following categories were assessed: 1) maximum T stage; 2) presence of benign mucosa; 3) presence of a precursor lesion; 4) highest tumor volume; 5) presence of lymphovascular invasion(LVI). In cases where a given category was demonstrated in >1 section, the section with the highest sTB was used. High risk features (HFR) included T4, <12 lymph nodes, positive margin, high grade tumor, perineural invasion and LVI. Pearson’s correlation was performed to compare two groups using a p-value of <0.05. Results 147 cases were examined. fTB was 1=25.2%, 2=40.8% and 3=34%. 63 tumors involved the left colon and 62 had nodal disease. Of 119 cases with known MMR status 44 were MMR deficient. sTB was uniform across the categories in 101(68.7%) and uneven in 46(32.3%) cases. 12(24.5%) of 49 stage II CRC without HRF showed uneven sTB, with 2 showing 2-tier discrepancy (sTB1, fTB3). sTB was highest for category 3 (94.1%, P<.001), followed by category 2 (91.8%, P<.001), and lowest for category 1 (82.3%, P<.001), which remained true after subgrouping by MMR status and tumor location. Conclusion While about 70% of cases showed uniform TB grading across categories, choosing the slide(s) with a precursor lesion or benign mucosa increases the probability of correctly grading TB. Given the management implication, it may be prudent to scan all tumor slides in stage II CRC without HRF to avoid under-grading of TB.

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Lymphovascular Invasion and Perineural Invasion Negatively Impact Overall Survival for Stage II Adenocarcinoma of the Colon

Diseases of the Colon & Rectum ◽

10.1097/dcr.0000000000001258 ◽

2019 ◽

Vol 62 (2) ◽

pp. 181-188 ◽

Cited By ~ 13

Author(s):

Matthew Skancke ◽

Suzanne M. Arnott ◽

Richard L. Amdur ◽

Robert S. Siegel ◽

Vincent J. Obias ◽

...

Keyword(s):

Overall Survival ◽

Lymphovascular Invasion ◽

Perineural Invasion ◽

Stage Ii ◽

Adenocarcinoma Of The Colon

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The Length of Peri-Neural Spreading in Clinically Mandibular Invaded Oral Cavity Squamous Cell Carcinoma

Journal of the Medical Association of Thailand ◽

10.35755/jmedassocthai.2020.05. ◽

2020 ◽

pp. 459-464

Keyword(s):

Squamous Cell Carcinoma ◽

Oral Cavity ◽

Cell Carcinoma ◽

Squamous Cell ◽

Lymphovascular Invasion ◽

Perineural Invasion ◽

Inferior Alveolar Nerve ◽

Surgical Margin ◽

Neural Invasion ◽

Resected Margin

Background: The objective of surgical management of oral squamous cell carcinoma (OSCC) is adequate resection with a clear margin. However, there is still a debate as to the optimal length for a mandibular resected margin. Objective: To examine the length of peri-neural spreading in T4 mandibular invaded oral cavity squamous cell carcinoma. Materials and Methods: Twenty-eight T4 pathological OSCC specimens that involved mandible and serial slices were studied and the length of tumor spreading along the inferior alveolar nerve (IAN) was determined. Tumor characteristics, risk factors, and survival were analyzed. Results: The incidence of peri-neural invasion was 11.11%, and IAN invasion was found in 14.29% of the tumor-invaded mandibular marrow. The length of tumor spreading along IAN was 3 to 12 mm. Poor prognostic factors of T4 OSCC were it being located on the tongue (HR 14.16), was pathological N2-3 (HR 31.05), and had high-risk features such as peri-neural invasion, lymphovascular invasion, and extra-nodal extension. Conclusion: A mandibular resected margin of at least 18 mm is recommended as a clear surgical margin in cases of T4 mandibular invasion OSCC. Keywords: Oral cancer, Perineural invasion, Inferior alveolar nerve, Squamous cell carcinoma, Mandibulectomy

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Prognostic Impact of Fusobacterium nucleatum Depends on Combined Tumor Location and Microsatellite Instability Status in Stage II/III Colorectal Cancers Treated with Adjuvant Chemotherapy

Journal of Pathology and Translational Medicine ◽

10.4132/jptm.2018.11.29 ◽

2019 ◽

Vol 53 (1) ◽

pp. 40-49 ◽

Cited By ~ 12

Author(s):

Hyeon Jeong Oh ◽

Jung Ho Kim ◽

Jeong Mo Bae ◽

Hyun Jung Kim ◽

Nam-Yun Cho ◽

...

Keyword(s):

Adjuvant Chemotherapy ◽

Microsatellite Instability ◽

Fusobacterium Nucleatum ◽

Tumor Location ◽

Stage Ii ◽

Colorectal Cancers ◽

Prognostic Impact ◽

Combined Tumor

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Inflammatory cytokines and distant recurrence in HER2-negative early breast cancer in the ECOG-ACRIN 5103 trial.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.520 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 520-520

Author(s):

Joseph A. Sparano ◽

Anne M. O'Neill ◽

Noah Graham ◽

Donald W. Northfelt ◽

Chau T. Dang ◽

...

Keyword(s):

Breast Cancer ◽

Adjuvant Chemotherapy ◽

Propensity Score ◽

Propensity Score Matching ◽

Early Breast Cancer ◽

Inflammatory Cytokines ◽

Multiple Testing ◽

Distant Recurrence ◽

Stage Ii ◽

P Value

520 Background: Systemic inflammation may contribute to cancer progression (PMC2803035), including recurrence of early breast cancer (PMC4828958). We hypothesized that inflammatory cytokines and/or chemokines may be associated with distant recurrence (DR). Methods: We performed a case:control study in women with stage II-III Her2-negative breast cancer, all of whom had surgery and adjuvant chemotherapy (doxorubicin/cyclophosphamide, then weekly paclitaxel) with/without bevacizumab, plus endocrine therapy if ER-positive (PMC6118403). Propensity score matching was used to identify approximately 250 case:control pairs (with/without DR). Serum samples obtained before adjuvant chemotherapy were analyzed using the MSD V-Plex Human Cytokine 36-Plex Kit for detection of human cytokines and chemokines involved in the Th1/Th2 pathway, chemotaxis, the Th17 pathway, angiogenesis, and immune system regulation. Conditional logistic regression analysis, with models fit via maximum likelihood, were used to estimate hazard ratios (HRs) and test for associations. Due to skewed nature of cytokines, HRs are reported on log base 2 scale. If adjusted for multiple testing including 36 markers, a p value of < 0.0014 would be required for statistical significance. Results: A total 249 matched pairs (498 patients) were identified. Covariates used for propensity score matching included age, menopausal status (post 54% vs. pre/peri 46%), ER/PR status (one/both pos 64% vs. both neg 36%) tumor size ( < = 2cm 17%, > 2-5cm 67%, > 5cm 16%) nodal status (neg 15%,1-3+ 32%, 4+ 53%), and grade (low 3%, int. 31%, high 66%). The only biomarker associated with a significantly increased DR risk when adjusted for multiple testing was the proinﬂammatory cytokine IL-6 (HR 1.37, 95% confidence intervals [CI] 1.15, 1.65, p = 0.0006). Others associated with a 2-sided p value < 0.05 included the chemokine MDC(macrophage-derived chemokine/CCL22) (1.90, 95% CI 1.17, 3.1, p = 0.0098), the T helper cell inﬂammatory cytokine IL-17A (HR 1.36, 95% CI 1.10, 1.67, p = 0.0052), and the cytokine VEGF-A (HR 1.13 for, 95% CI 1.01, 1.27, p = 0.037). There was no statistical interaction between VEGF-A and bevacizumab benefit. The median and mean value for IL-6 was 0.95 and 7.5 pg/ml (range 0.04-2761.24 pg/ml). Conclusions: This analysis provides level 1B evidence indicating that higher levels of the cytokine IL-6 at diagnosis are associated with a significantly higher DR risk in high-risk stage II-III breast cancer despite optimal adjuvant systemic therapy. This provides a foundation for confirmatory validation of IL-6 as a prognostic biomarker, and potentially as a predictive biomarker for testing therapeutic interventions targeting the IL-6/JAK/STAT3 pathway. Supported by NCI U10CA180820,180794,180821; UG1CA189859,232760,233290, 233196; Komen Foundation; Breast Cancer Research Foundation. Clinical trial information: NCT00433511.

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THE INFLUENCE OF VOLUMETRIC TUMOR DOUBLING TIME ON SURVIVAL OF PATIENTS WITH INTRACRANIAL TUMORS

10.36106/ijsr/4104261 ◽

2021 ◽

pp. 39-43

Author(s):

Yadav Ambica ◽

Tandon Anupama

Keyword(s):

Prognostic Factors ◽

Doubling Time ◽

Tumor Volume ◽

Histological Grade ◽

Tumor Location ◽

P Value ◽

Intracranial Tumors ◽

Excellent Correlation ◽

Tumor Doubling Time ◽

Initial Tumor

Objective:To evaluate inuence of volumetric tumor doubling time on survival of patients with intracranial tumors. Study design: 20 patients with intracranial tumor of either sex and any age were included, if two imaging scans were available/could be done in which change in tomor volume was appreciable and the tumor margins were well demarcated. Based on change in tumor volume, tumor doubling time (DT) and predictive survival time (PST) were calculated. Patients were followed up for 6 months or longer for actual survival time (AST). Results: The histological grade was found to have a signicant correlation with DT (P value 0.046) and PST of the tumor (P value 0.038). DT and PSTwere found to be signicantly lower in high grade astrocytomas. Age, gender, tumor location and initial tumor volume were not found to have a signicant correlation with DTand PST. When DTwas compared to PST, excellent correlation was seen which was statistically signicant (Pvalue < 0.001) and suggested a linear relationship. Conclusion: Computed Tomography (CT) & Magnetic Resonance Imaging (MRI) can accurately dene the intracranial tumors and can reliably measure their volume. Calculation of tumor volume, change in tumor volume, DT and PST based on imaging studies is easy and reproducible. DT and PST have an excellent correlation & there is a linear relationship between the two. Histological grade and DT are the signicant prognostic factors while age, gender, tumor location and initial tumor volume are not signicant prognostic factors in patients with brain tumors.

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Mutational Profile of Driver Genes in Brazilian Melanomas

Journal of Global Oncology ◽

10.1200/jgo.19.00169 ◽

2019 ◽

pp. 1-14 ◽

Cited By ~ 1

Author(s):

Anna Luiza S.A. Vicente ◽

Camila S. Crovador ◽

Graziela Macedo ◽

Cristovam Scapulatempo-Neto ◽

Rui M. Reis ◽

...

Keyword(s):

Skin Color ◽

Hot Spot ◽

Survival Rates ◽

Tumor Location ◽

Superficial Spreading ◽

Driver Genes ◽

Tert Promoter ◽

Mutational Status ◽

Black Skin ◽

Anatomic Locations

PURPOSE Mutation testing of the key genes involved in melanoma oncogenesis is now mandatory for the application of targeted therapeutics. However, knowledge of the mutational profile of melanoma remains largely unknown in Brazil. PATIENTS AND METHODS In this study, we assessed the mutation status of melanoma driver genes BRAF, NRAS, TERT, KIT, and PDGFRA in a cohort of 459 patients attended at Barretos Cancer Hospital between 2001 and 2012. We used polymerase chain reaction followed by Sanger sequencing to analyze the hot spot mutations of BRAF exon 15 (V600E), NRAS (codons 12/13 and 61), TERT (promoter region), KIT (exons 9, 11, 13, and 17), and PDGFRA (exons 12, 14, and 18) in tumors. The mutational profile was investigated for associations with demographic, histopathologic, and clinical features of the disease. RESULTS The nodular subtype was most frequent (38.9%) followed by the superficial spreading subtype (34.4%). The most frequent tumor location was in the limbs (50.0%). The mutation rates were 34.3% for TERT and 34.1% for BRAF followed by NRAS (7.9%), KIT (6.2%), and PDGFRA (2.9%). The BRAF ( P = .014) and TERT ( P = .006) mutations were associated with younger patients and with different anatomic locations, particularly in the trunk, for the superficial spreading and nodular subtypes, respectively ( P = .0001 for both). PDGFRA mutations were associated with black skin color ( P = .023) and TERT promoter mutations with an absence of ulceration ( P = .037) and lower levels of lactate dehydrogenase. There was no association between patient survival rates and mutational status. CONCLUSION The similar mutational profile we observe in melanomas in Brazil compared with other populations will help to guide precision medicine in this country.

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What are the contextual risk factors for low colorectal cancer screening uptake in El Paso County, Texas? Spatial cross-sectional analysis

BMJ Open ◽

10.1136/bmjopen-2020-038342 ◽

2020 ◽

Vol 10 (10) ◽

pp. e038342

Author(s):

Jennifer Salinas ◽

Jacquelyn Brito ◽

Cheyenne Rincones ◽

Navkiran K Shokar

Keyword(s):

Colorectal Cancer ◽

Census Tract ◽

Hot Spot ◽

El Paso ◽

P Value ◽

Hot Spot Analysis ◽

Crc Screening ◽

Screening Uptake ◽

Fit Testing ◽

Spot Analysis

ObjectiveThis study examines the geographical and socioeconomic factors associated with uptake of colorectal cancer (CRC) screening (colonoscopies or faecal immunochemical test (FIT) testing).DesignSecondary data analysis.SettingThe Against Colorectal Cancer in our Community (ACCION) programme was implemented in El Paso County, Texas, to increase screening rates among the uninsured and underinsured.ParticipantsWe successfully geocoded 5777 who were offered a free colonoscopy or FIT testing kit.Primary outcome measureCensus-tract CRC screening uptake average.ResultsMedicare recipient mortality (β=0.409, p-value=0.049) and % 65 years or older (β=−0.577, p value=0.000) were significant census tract contextual factors that were associated with the prevalence of CRC screening uptake in the geographically weighted Poisson regression. Neither Latino ethnicity nor immigrant concentration were significant predictors of CRC screening uptake in the ACCION programme. Hot spot analysis demonstrated that there was a significant low-value cluster in South Central El Paso. There was a similar hot spot for % 65 years or older in this same area, suggesting that uptake was lowest in an area that had the highest concentration of older adults.ConclusionThe results from this study revealed not only feasibility of hot spot analysis but also its utility in geographically tracking successful CRC screening uptake in cancer prevention and intervention programmes.

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