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

685 Background: Presence of lymphovascular invasion (LVI) is known to be a predictor of lymph node involvement in colon adenocarcinoma (CA). Lymph node involvement is associated with poorer prognosis necessitating adjuvant therapy. While some studies have suggested that LVI is a predictor of worse overall survival in early stage colon cancer, the significance of LVI on prognosis has not been tested in a comprehensive North American data set. Methods: Patients with stage II and III CA with LVI data available and those who received predefined standard of care treatment were identified from the National Cancer Data Base (NCDB) from 2011 to 2015. The relationship between LVI and overall survival was tested using Kaplan-Meier survival curves and Cox proportional hazards regression analysis after adjusting for relevant clinical and demographic variables. Hazard ratios and 95% confidence intervals are reported along with median overall survival (OS) where available. Results: The dataset included 93,070 patients with stage II and 66,701 patients with stage III CA. The proportion of patients with LVI was 13% in stage II and 47% in stage III CA. After adjusting for age, sex, gender, race, comorbidities, socioeconomic status, T, and N stage, LVI was associated with worse OS in stage II, HR 1.2 (1.15-1.25, p < 0.001), and in stage III, HR 1.25 (1.21-1.30, p < 0.001), CA. Median OS was 6.51 years with LVI versus. 6.85 years without LVI in stage II compared with 6.57 years with LVI versus not reached without LVI in stage III CA. Of the stage II patients with LVI, 20% received adjuvant chemotherapy (CT) and median OS was 6.91 years for those who did versus 6.07 years for those who did not receive CT. Conclusions: Our data suggest that LVI is an important predictor of OS in stage II and III CA. There is evidence that adjuvant chemotherapy improves OS in advanced CA but there remains uncertainty as to the benefit in stage II. Despite this uncertainty, guidelines suggest consideration of adjuvant CT in patients with high-risk stage II disease. Our data support the recommendation that LVI be considered a high-risk feature in stage II disease. Further studies are necessary to examine whether the type or duration of CT should differ for patients with CA and LVI.

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Stage II and III rectal adenocarcinoma outcomes related to lymphovascular invasion.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.4_suppl.698 ◽

2019 ◽

Vol 37 (4_suppl) ◽

pp. 698-698

Author(s):

Shalana BL O'Brien ◽

Dorotea Mutabdzic ◽

Elizabeth A. Handorf ◽

Karthik Devarajan ◽

Sanjay S. Reddy ◽

...

Keyword(s):

Rectal Cancer ◽

Overall Survival ◽

Cancer Patients ◽

Median Overall Survival ◽

Lymphovascular Invasion ◽

Rectal Adenocarcinoma ◽

Stage Ii ◽

Stage Iii ◽

Good Survival ◽

Cancer Data

698 Background: Lymphovascular invasion (LVI) has been shown to be associated with nodal involvement and higher rates of local recurrence in rectal cancer. In some studies, the presence of LVI has also been associated with worse overall survival; however, these have been mostly smaller, single institution studies or incomplete data sets. Our goal was to examine the effect of LVI on prognosis in a large and inclusive database. Methods: Outcomes of patients with clinical stage II and stage III rectal adenocarcinoma in the National Cancer Data Base (NCDB) from 2011 to 2015, in whom LVI data was available, were included. Exclusion criteria incorporated patients who did not receive neoadjuvant radiation and chemotherapy, neoadjuvant or adjuvant. Overall survival was compared in patients with and without LVI, controlling for age, sex, race, comorbidities, socioeconomic factors, and T and N stages using Kaplan-Meier survival curves and Cox proportional hazards regression analysis. Median overall survival and hazard ratios with 95% confidence intervals are reported where available. Results: The dataset included 9206 patients with stage II and 12640 patients with stage III rectal adenocarcinoma for which LVI data were available and who received the study’s previously defined standard of care. The proportion of patients with LVI was 11% in stage II and 16% in stage III rectal cancer. After adjusting for age, sex, race, T or N stage, and other clinical and demographic variables, LVI was associated with worse overall survival in stage II HR 1.87 (1.62-2.16, p < 0.001) and in stage III HR 1.8 (1.61-2.02, p < 0.001) rectal cancer. The median overall survival was not reached in stage II rectal cancer patients without LVI versus 5.73 years with LVI. In stage III rectal cancer, the median overall survival was 6.91 years without LVI versus 6.21 years with LVI. Conclusions: Lymphovascular invasion is an independent risk factor of mortality in stage II and III rectal cancer. Stage II rectal cancer patients without LVI have comparatively good survival of the groups studied, potentially identifying a group of patients that may benefit from de-escalated therapy. Further studies will be guided at identifying if benefits with chemotherapy are associated with LVI status.

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Important Prognostic Factors in Adenocarcinoma of the Ampulla of Vater

The American Surgeon ◽

10.1177/000313480907500904 ◽

2009 ◽

Vol 75 (9) ◽

pp. 754-761 ◽

Cited By ~ 8

Author(s):

Michael C. Lowe ◽

Ipek Coban ◽

N. Volkan Adsay ◽

Juan M. Sarmiento ◽

Carrie K. Chu ◽

...

Keyword(s):

Overall Survival ◽

Lymphovascular Invasion ◽

Perineural Invasion ◽

Ampulla Of Vater ◽

Clinicopathologic Features ◽

Histological Subtype ◽

Ampullary Adenocarcinoma ◽

Poor Differentiation ◽

Predicting Outcome ◽

Mixed Histology

Ampullary adenocarcinoma (AmpCA) carries a better overall survival (OS) rate than other periampullary cancers. We examined clinicopathologic features in AmpCA for impact on OS. Records of patients undergoing pancreaticoduodenectomy from 2000 to 2007 for AmpCA were reviewed and histological specimens were reanalyzed. Of 302 patients undergoing pancreaticoduodenectomy for malignancy, 45 (14.9%) had AmpCA. Mean age was 61.3 ± 12.2 years, mean tumor size was 2.6 ± 1.3 cm, 57 per cent were ≥ T3 tumors, 42 per cent were N1 stage, 13 (49%) had perineural invasion (PNI), and 29 (64%) had lymphovascular invasion (LVI). Thirteen were intestinal (29%), 14 were pancreaticobiliary (31%), and 18 were mixed (40%). Median OS was 42 months (range 4-80 mos). On log rank testing, ≥ T3 (24 vs 65 mos, P < 0.01), N1 (25 vs 61 mos, P < 0.01), poor differentiation (24 vs 44 mos, P = 0.01), pancreaticobiliary subtype (23 vs 44 mos, P = 0.01), and PNI (23 vs 44 mos, P < 0.01) were significant for worse survival. By multivariate analysis, N1 disease (hazard ratio [HR] 4.50,95% confidence interval [CI] 1.16-17.40) and PNI (HR 4.62, CI 1.11-19.21) maintained associations with worse survival, whereas histological subtype did not. N1 disease and presence of PNI demonstrated independent associations with worse survival. Given high percentage of mixed histology, PNI may be more informative than the subtype in predicting outcome for patients with AmpCA.

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

American Journal of Clinical Pathology ◽

10.1093/ajcp/aqaa161.329 ◽

2020 ◽

Vol 154 (Supplement_1) ◽

pp. S150-S151

Author(s):

M Aldyab ◽

S Najjar ◽

J V Rand ◽

H Lee

Keyword(s):

Lymphovascular Invasion ◽

Perineural Invasion ◽

Hot Spot ◽

Positive Margin ◽

Tumor Location ◽

Consensus Conference ◽

Stage Ii ◽

P Value ◽

Precursor Lesion ◽

Management Implication

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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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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Propensity score‐matched comparison of stenting as a bridge to surgery and emergency surgery for acute malignant left‐sided colonic obstruction

BMC Surgery ◽

10.1186/s12893-021-01144-z ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Yuepeng Cao ◽

Qing Chen ◽

Zhizhan Ni ◽

Feng Wu ◽

Chenshen Huang ◽

...

Keyword(s):

Overall Survival ◽

Propensity Score ◽

Emergency Surgery ◽

Perineural Invasion ◽

Cox Regression ◽

Colonic Obstruction ◽

Metal Stents ◽

Bridge To Surgery ◽

Cox Regression Analysis ◽

Self Expanding Metal Stents

Abstract Background Bridge to elective surgery (BTS) using self-expanding metal stents (SEMSs) is a common alternative to emergency surgery (ES) for acute malignant left-sided colonic obstruction (AMLCO). However, studies regarding the long-term impact of BTS are limited and have reported unclear results. Methods A multicenter observational study was performed at three hospitals from April 2012 to December 2019. Propensity score matching (PSM) was introduced to minimize selection bias. The primary endpoint was overall survival. The secondary endpoints included surgical approaches, primary resection types, total stent-related adverse effects (AEs), surgical AEs, length of hospital stay, 30-day mortality and tumor recurrence. Results Forty-nine patients in both the BTS and ES groups were matched. Patients in the BTS group more often underwent laparoscopic resection [31 (63.3%) vs. 8 (16.3%), p < 0.001], were less likely to have a primary stoma [13 (26.5%) vs. 26 (53.1%), p = 0.007] and more often had perineural invasion [25 (51.0 %) vs. 13 (26.5 %), p = 0.013]. The median overall survival was significantly lower in patients with stent insertion (41 vs. 65 months, p = 0.041). The 3-year overall survival (53.0 vs. 77.2%, p = 0.039) and 5-year overall survival (30.6 vs. 55.0%, p = 0.025) were significantly less favorable in the BTS group. In multivariate Cox regression analysis, stenting (hazard ratio(HR) = 2.309(1.052–5.066), p = 0.037), surgical AEs (HR = 1.394 (1.053–1.845), p = 0.020) and pTNM stage (HR = 1.706 (1.116–2.607), p = 0.014) were positively correlated with overall survival in matched patients. Conclusions Self-expanding metal stents as “a bridge to surgery” are associated with more perineural invasion, a higher recurrence rate and worse overall survival in patients with acute malignant left-sided colonic obstruction compared with emergency surgery.

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Association of chemotherapy with survival in stage II colon cancer patients who received radical surgery: a retrospective cohort study

BMC Cancer ◽

10.1186/s12885-021-08057-3 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Zhihao Lv ◽

Yuqi Liang ◽

Huaxi Liu ◽

Delong Mo

Keyword(s):

Colon Cancer ◽

Overall Survival ◽

Cancer Patients ◽

Prediction Models ◽

Radical Surgery ◽

Survival Rates ◽

Stage Ii ◽

Survival Prediction ◽

Stage Ii Colon Cancer ◽

Overall Survival Rates

Abstract Background It remains controversial whether patients with Stage II colon cancer would benefit from chemotherapy after radical surgery. This study aims to assess the real effectiveness of chemotherapy in patients with stage II colon cancer undergoing radical surgery and to construct survival prediction models to predict the survival benefits of chemotherapy. Methods Data for stage II colon cancer patients with radical surgery were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. Propensity score matching (1:1) was performed according to receive or not receive chemotherapy. Competitive risk regression models were used to assess colon cancer cause-specific death (CSD) and non-colon cancer cause-specific death (NCSD). Survival prediction nomograms were constructed to predict overall survival (OS) and colon cancer cause-specific survival (CSS). The predictive abilities of the constructed models were evaluated by the concordance indexes (C-indexes) and calibration curves. Results A total of 25,110 patients were identified, 21.7% received chemotherapy, and 78.3% were without chemotherapy. A total of 10,916 patients were extracted after propensity score matching. The estimated 3-year overall survival rates of chemotherapy were 0.7% higher than non- chemotherapy. The estimated 5-year and 10-year overall survival rates of non-chemotherapy were 1.3 and 2.1% higher than chemotherapy, respectively. Survival prediction models showed good discrimination (the C-indexes between 0.582 and 0.757) and excellent calibration. Conclusions Chemotherapy improves the short-term (43 months) survival benefit of stage II colon cancer patients who received radical surgery. Survival prediction models can be used to predict OS and CSS of patients receiving chemotherapy as well as OS and CSS of patients not receiving chemotherapy and to make individualized treatment recommendations for stage II colon cancer patients who received radical surgery.

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Digital Immunophenotyping Predicts Disease Free and Overall Survival in Early Stage Melanoma Patients

Cells ◽

10.3390/cells10020422 ◽

2021 ◽

Vol 10 (2) ◽

pp. 422

Author(s):

Francesco De Logu ◽

Francesca Galli ◽

Romina Nassini ◽

Filippo Ugolini ◽

Sara Simi ◽

...

Keyword(s):

Overall Survival ◽

T Cells ◽

Cd8 T Cells ◽

Early Stage ◽

High Density ◽

Stage Ii ◽

Prognostic Impact ◽

Training Cohort ◽

Melanoma Patients ◽

Disease Free

Background: the prognostic significance of tumor infiltrating lymphocytes (TILs) in intermediate/thick primary cutaneous melanoma (PCM) remains controversial, partially because conventional evaluation is not reliable, due to inter-observer variability and diverse scoring methods. We aimed to assess the prognostic impact of the density and spatial distribution of immune cells in early stage intermediate/thick PCM. Materials and Methods: digital image acquisition and quantitative analysis of tissue immune biomarkers (CD3, CD4, CD8, CD68, PD-L1, CD163, FOX-P3, and PD-1) was carried out in a training cohort, which included patients with primary PCM ≥ 2 mm diagnosed, treated, and followed-up prospectively in three Italian centers. Results were validated in an independent Italian cohort. Results: in the training cohort, 100 Stage II–III melanoma patients were valuable. At multivariable analysis, a longer disease free survival (DFS) was statistically associated with higher levels of CD4+ intratumoral T-cells (aHR [100 cell/mm2 increase] 0.98, 95%CI 0.95–1.00, p = 0.041) and CD163+ inner peritumoral (aHR [high vs. low] 0.56, 95%CI 0.32–0.99, p = 0.047). A statistically significant longer DFS (aHR [high-high vs. low-low] 0.52, 95%CI 0.28–0.99, p = 0.047) and overall survival (OS) (aHR [high-high vs. low-low] 0.39, 95%CI 0.18–0.85, p = 0.018) was found in patients with a high density of both intratumoral CD8+ T-cells and CD68+ macrophages as compared to those with low density of both intratumoral CD8+ T-cells and CD68+ macrophages. Consistently, in the validation cohort, patients with high density of both intratumoral CD8+ and CD3+ T-cells were associated to a statistically better DFS (aHR[high-high vs. low-low] 0.24, 95%CI 0.10–0.56, p < 0.001) and those with high density of both intratumoral CD8+ and CD68+ were associated to a statistically longer OS (aHR[high-high vs. low-low] 0.28, 95%CI 0.09–0.86, p = 0.025). Conclusion: our findings suggest that a specific preexisting profile of T cells and macrophages distribution in melanomas may predict the risk of recurrence and death with potential implications for the stratification of stage II–III melanoma patients.

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Gastric Cancer Treatments and Survival Trends in the United States

Current Oncology ◽

10.3390/curroncol28010017 ◽

2020 ◽

Vol 28 (1) ◽

pp. 138-151

Author(s):

Kelly A. Stahl ◽

Elizabeth J. Olecki ◽

Matthew E. Dixon ◽

June S. Peng ◽

Madeline B. Torres ◽

...

Keyword(s):

Gastric Cancer ◽

Overall Survival ◽

Stage Iv ◽

The United States ◽

Current Treatment ◽

Stage I ◽

Stage Ii ◽

Chi Square ◽

Specific Guideline ◽

Kaplan Meier

Gastric cancer is the third most common cause of cancer deaths worldwide. Despite evidence-based recommendation for treatment, the current treatment patterns for all stages of gastric cancer remain largely unexplored. This study investigates trends in the treatments and survival of gastric cancer. The National Cancer Database was used to identify gastric adenocarcinoma patients from 2004–2016. Chi-square tests were used to examine subgroup differences between disease stages: Stage I, II/III and IV. Multivariate analyses identified factors associated with the receipt of guideline concordant care. The Kaplan–Meier method was used to assess three-year overall survival. The final cohort included 108,150 patients: 23,584 Stage I, 40,216 Stage II/III, and 44,350 Stage IV. Stage specific guideline concordant care was received in only 73% of patients with Stage I disease and 51% of patients with Stage II/III disease. Patients who received guideline consistent care had significantly improved survival compared to those who did not. Overall, we found only moderate improvement in guideline adherence and three-year overall survival during the 13-year study time period. This study showed underutilization of stage specific guideline concordant care for stage I and II/III disease.

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