Novel Prognostic Factors in Resected Small Bowel Adenocarcinoma

430 Background: Small bowel adenocarcinoma (SBA) is a rare disease. Previous studies suggested several prognostic factors of unresectable SBA, including age, performance status (PS), primary site, resection of primary tumor, histology, and tumor marker (CEA and CA19–9) levels. However, prognostic factors of the patients treated with oxaliplatin–fluoropyrimidine combination therapy were unknown, while these drugs were reported as a promising chemotherapy regimen for SBA. Methods: Previously untreated SBA patients were treated with an mFOLFOX6 regimen, and a post hoc analyses for prognostic factors were performed. Results: Between April 2010 and November 2012, 24 patients were included in this study. The overall response rate was 45% (9/20). The median progression-free survival and overall survival (OS) were 5.4 months (95% CI, 4.8–6.0) and 17.3 months (95% CI, 11.7–19.0), respectively. Univariate analysis revealed that lower PS (HR= 0.27; 95% CI, 0.10–0.77; p= 0.014), primary disease of the jejunum (HR= 0.35; 95% CI, 0.11–1.12; p=0.077), and serum CEA in the normal range (HR= 0.40; 95% CI, 0.14–1.11; p= 0.079) were potential prognostic factors of longer OS (threshold, p< 0.10). Although resection of the primary tumor was not a predictive factor of survival in this study, 54% and 21% of the patients needed surgery (primary resection or bypass) because of stenosis before and during chemotherapy, respectively. It is considered that bowel obstruction should be addressed before and during treatment. Conclusions: PS, primary site, and serum CEA levels are potential prognostic factors of unresectable SBA. There is a higher incidence of bowel stenosis or obstruction caused by the primary tumor before and during the treatment of SBA.

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Lymphocyte-to-monocyte ratio and neutrophil-to-lymphocyte ratio independently predict survival in resected small bowel adenocarcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.4_suppl.426 ◽

2019 ◽

Vol 37 (4_suppl) ◽

pp. 426-426

Author(s):

Brandon M. Huffman ◽

Shruti Patel ◽

Siddhartha Yadav ◽

Zhaohui Jin ◽

Amit Mahipal

Keyword(s):

Overall Survival ◽

Multivariate Analysis ◽

Small Bowel ◽

Tumor Size ◽

Neutrophil To Lymphocyte Ratio ◽

Stage I ◽

Small Bowel Adenocarcinoma ◽

Lymphocyte Ratio ◽

Lymphocyte To Monocyte Ratio ◽

Resected Small Bowel

426 Background: Small bowel adenocarcinoma is a rare malignancy affecting approximately 2,000 patients per year. There is a paucity of evidence prognosticating patients with small bowel adenocarcinoma. We aimed to evaluate multiple factors in patients with resected small bowel adenocarcinoma to determine any association with survival outcomes. Methods: Ninety three patients who underwent resection for stage I-III small bowel adenocarcinoma were retrospectively identified utilizing the pathology database at a single tertiary referral institution. All patients had complete follow up data and were included in the survival analysis. JMP software was used for statistical analysis. Overall survival was performed utilizing Kaplan-Meier method, and log-rank tests were used for statistical comparisons. Cox proportional hazards were performed to control for age, gender, location of tumor, tumor size, tumor stage, and adjuvant therapy. Sensitivity analysis was performed to establish best cutoff points for continuous variables. All tests were two sided and a P value of < 0.05 was considered significant. Results: The median age at diagnosis was 65 years (range 32-90). 61% were male. Median tumor size was 4.5 cm. There were 20, 36, and 37 patients with stage I, stage II, and stage III disease, respectively. Median overall survival (OS) was 151 months, 104 months, and 44 months for stages I, II, and III disease. In a multivariate analysis, independent predictor factors included presurgical lymphocyte to monocyte ratio (LMR) > 4.0, with a Hazard Ratio (HR) 0.13 (95% CI 0.007-0.69, p = 0.01), presurgical neutrophil to lymphocyte ratio (NLR) < 8.0, HR 0.39 (95% CI 0.17-0.96, p = 0.04), and tumor size < 7.5 cm, HR 0.22 (95% CI 0.07-0.85, p = 0.03). Stage, age, T stage, and N stage influenced overall survival in univariate analysis, but were not statistically significant on multivariate analysis. Conclusions: LMR and NLR independently predict survival in patients with resected small bowel adenocarcinoma.

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Prognostic Factors of Primary Small Bowel Adenocarcinoma: Univariate and Multivariate Analysis

World Journal of Surgery ◽

10.1007/s00268-005-7898-6 ◽

2006 ◽

Vol 30 (3) ◽

pp. 391-398 ◽

Cited By ~ 56

Author(s):

Ting-Jung Wu ◽

Chun-Nan Yeh ◽

Tzu-Chieh Chao ◽

Yi-Yin Jan ◽

Miin-Fu Chen

Keyword(s):

Multivariate Analysis ◽

Prognostic Factors ◽

Small Bowel ◽

Small Bowel Adenocarcinoma ◽

Primary Small Bowel

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6603 POSTER Prognostic Factors of 127 Patients With Advanced Small-bowel Adenocarcinoma Treated With Systemic Chemotherapy

European Journal of Cancer ◽

10.1016/s0959-8049(11)71914-1 ◽

2011 ◽

Vol 47 ◽

pp. S472-S473

Author(s):

Y. Homma ◽

M. Taguri ◽

N. Boku ◽

T. Tsushima ◽

H. Takahashi ◽

...

Keyword(s):

Prognostic Factors ◽

Small Bowel ◽

Systemic Chemotherapy ◽

Small Bowel Adenocarcinoma

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Validation of lymphocyte to monocyte ratio in resected small bowel adenocarcinoma as a predictor of survival.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e15799 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e15799-e15799

Author(s):

Brandon M. Huffman ◽

Zhaohui Jin ◽

Siddhartha Yadav ◽

Shruti Patel ◽

Amit Mahipal ◽

...

Keyword(s):

Overall Survival ◽

Prognostic Factor ◽

Small Bowel ◽

Predictive Value ◽

P Value ◽

Small Bowel Adenocarcinoma ◽

Training Set ◽

Lymphocyte To Monocyte Ratio ◽

Negative Prognostic Factor ◽

Resected Small Bowel

e15799 Background: Lymphocyte to monocyte ratio (LMR) has been described as a prognostic factor in many solid tumors including colorectal adenocarcinoma. LMR has not been investigated as a prognostic factor in small bowel cancers. In this study, we aimed to evaluate prognostic factors in resected small bowel adenocarcinoma including LMR. Methods: Two hundred forty-one patients who underwent resection for stage I-III small bowel adenocarcinoma were retrospectively identified utilizing the pathology database at a single tertiary referral institution from 1994 to 2015. All patients had complete follow up data and were included in the survival analysis. One hundred sixty-nine patients had preoperative peripheral blood counts available for analysis. Plot of martingale residuals against LMR were used to establish best cutoff points for LMR. A training set for LMR included consecutively identified patients from 2006 to 2015, and a validation cohort including patients identified from 1994 to 2005 was used. Overall survival was performed utilizing Kaplan-Meier method, and Wilcoxon tests were used for statistical comparisons. Cox proportional hazards were performed and all tests were two sided. P value of < 0.05 was considered significant. Results: Median overall survival for the entire group was 54.5 months (95% CI: 37.2-81.2 months) with 5- and 10-year overall survival of 48% and 35%. The training set for LMR included 81 patients, and the validation set included 88 patients. The cutoff of 1.56 was chosen based on most significant p value (p = 0.002). When combined, the overall area under the curve (AUC) for LMR was 0.63, p < 0.01, (specificity 37.3%, sensitivity 90.1%, positive predictive value 33.1%, and negative predictive value 92.2%). There were 126 patients with LMR > 1.56 and 43 patients with LMR < 1.56 in the entire cohort. In multivariate analysis, LMR under 1.56 was a negative prognostic factor, HR = 2.20 (95% CI: 1.27-3.84, p < 0.01). In addition to LMR, age > 60 years and advanced T stage were independently negative predictors of overall survival in all patients. Conclusions: Lymphocyte-to-monocyte ratio < 1.56 is a validated negative prognostic factor in resected small bowel adenocarcinoma.

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Adjuvant chemotherapy impact on the overall survival of completely resected small bowel adenocarcinoma: An updated meta-analysis.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e16806 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e16806-e16806

Author(s):

Philip A. Haddad ◽

Dalia A. Hammoud ◽

Kevin M. Gallagher

Keyword(s):

Overall Survival ◽

Adjuvant Chemotherapy ◽

Small Bowel ◽

Survival Benefit ◽

Randomized Clinical Trials ◽

Meta Analysis ◽

Adjuvant Chemoradiotherapy ◽

Small Bowel Adenocarcinoma ◽

The Impact ◽

Resected Small Bowel

e16806 Background: While the small intestine represents around 75% of the length and more than 90% of the gastrointestinal tract mucosal surface, it contributes around 2% of gastrointestinal tumors. Adenocarcinoma which constitutes 40% of all small bowel tumors is the most common histology. Complete surgical resection of early-stage small bowel adenocarcinoma (SBAC) is the only proven potentially curative therapy. Due to the rarity of this disease and the absence of randomized trials, the benefit of postoperative adjuvant chemotherapy (ACT) in patients with completely resected localized SBAC has been controversial. A meta-analysis conducted in 2018 found no survival benefit for adjuvant therapies in SBAC. However, this meta-analysis combined studies that used adjuvant chemotherapy and chemoradiotherapy and included studies contaminated by other less chemosensitive histologies and more advanced and sometimes metastatic disease. The purpose of this meta-analysis is to evaluate the impact of ACT on the overall survival (OS) of patients with completely resected SBAC incorporating more recent studies. Methods: A review of the medical literature was conducted using online databases. Inclusion criteria consisted of resected small bowel adenocarcinoma, English language, publications from 2000 to the present, and comparative studies reporting OS with hazard ratios (HR) or Kaplan-Meier curves of patients that underwent ACT versus those that did not. Adjuvant chemoradiotherapy studies and those that reported aggregate OS for a cohort with mixed histologies were excluded. A meta-analysis was conducted using an inverse variance method with a random-effects model. Results: Nine retrospective series which included 2082 patients were selected and analyzed. The majority of SBAC patients that received ACT belonged to stages II & III. ACT was found to be significantly associated with better OS in patients with completely resected SBAC (HR 0.66, 95%CI: 0.56-0.78, p < 0.001). Conclusions: This is the first meta-analysis to show that adjuvant chemotherapy is associated with a survival benefit in patients with completely resected small bowel adenocarcinoma. In the absence of randomized clinical trials, this meta-analysis represents the most compelling data supporting the use of ACT in this patient population.

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Primary small bowel adenocarcinoma: current view on clinical features, risk and prognostic factors, treatment and outcome

Scandinavian Journal of Gastroenterology ◽

10.1080/00365521.2017.1356932 ◽

2017 ◽

Vol 52 (11) ◽

pp. 1194-1202 ◽

Cited By ~ 7

Author(s):

Gustaw Lech ◽

Wojciech Korcz ◽

Emilia Kowalczyk ◽

Robert Słotwiński ◽

Maciej Słodkowski

Keyword(s):

Prognostic Factors ◽

Small Bowel ◽

Clinical Features ◽

Current View ◽

Small Bowel Adenocarcinoma ◽

Primary Small Bowel

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Invited Commentary to “Prognostic Factors of Primary Small Bowel Adenocarcinoma: Univariate and Multivariate Analysis”

World Journal of Surgery ◽

10.1007/s00268-005-1148-9 ◽

2006 ◽

Vol 30 (3) ◽

pp. 399-399

Author(s):

N. Joseph Espat

Keyword(s):

Multivariate Analysis ◽

Prognostic Factors ◽

Small Bowel ◽

Small Bowel Adenocarcinoma ◽

Primary Small Bowel

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Fifteen-year experience of all patients (pts) with small bowel adenocarcinoma (SBA), treated in a specialized gastrointestinal (GI) oncology unit: Royal Marsden (RM) experience.

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.3_suppl.316 ◽

2014 ◽

Vol 32 (3_suppl) ◽

pp. 316-316

Author(s):

Khurum Hayat Khan ◽

Clare Peckitt ◽

Francesco Sclafani ◽

Sachin Trivedi ◽

Vikram Kumar Jain ◽

...

Keyword(s):

Prognostic Factors ◽

Small Bowel ◽

Advanced Disease ◽

Early Stage ◽

Univariate Analysis ◽

Locally Advanced ◽

Small Bowel Adenocarcinoma ◽

Early Stage Disease ◽

Free Survival ◽

Resectable Disease

316 Background: Small bowel adenocarcinoma (SBA) is a rare tumour with poor prognosis. There is paucity of published literature due to rarity of disease; we conducted this retrospective study to determine the clinical course and outcome along with prognostic factors in both early and later stage SBA. Methods: Clinical characteristics and outcomes of all pts treated consecutively in the GI Unit RM, 1996-2011 were recorded. The study endpoints were relapse free survival (RFS), progression free survival (PFS), and overall survival (OS), in early stage pts (G1) and in pts with advanced disease (presentation or relapse with un-resectable disease=G2). In G2 response rate (RR) to chemotherapy was determined. In both groups association to baseline prognostic factors were sought by performing Cox regression univariate analysis (UVA). Results: Eighty four pts with SBA were treated 1996-2011. A total of 48 presented with early stage disease (G1). In G1 (58.3% males; mean age, 57 years), 44/48 pts underwent R0 resection; 21 received adjuvant chemotherapy. RFS, PFS and OS in this group were 29.6 [95% confidence interval (CI) 3.3-55.9], 31.1 (CI=8.0-54.3) and 42.9 (CI=0-94.9) months (m), with median follow up of 76.4 m. Poor histological differentiation (p=0.025), abnormal CEA at presentation (P=0.082), and lymphovascular invasion (p=0.003) were prognostic of OS. G2 comprised of 36 pts with un-resectable disease along with 23 from G1 who subsequently relapsed [G2 (n=59); 52.5% males; mean age, 59 years]; 54 pts with metastatic and 5 with locally advanced disease; 78% received first-line chemotherapy. Overall RR of pts who received chemotherapy was 50%. OS and PFS were 12.8 (CI =8.4-17.2) and 8.8 (CI=5.5-12.3) m respectively; 1-year survival was 60.9% vs. 27.3% (no chemotherapy) (p=0.042). Abnormal albumin (0.041), platelet count (p=0.007) and CEA (p=0.025) were prognostic of OS in the chemotherapy group; doublet (18/41) versus triplet (23/41) chemotherapy were not prognostic (p=0.185). Conclusions: Pts with SBA and metastatic disease may derive benefit from systemic chemotherapy; prospective clinical trials are required to evaluate this further.

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