Resected Small Bowel Adenocarcinoma Research Articles

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

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.

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

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.

An Examination of Lymph Node Sampling as a Predictor of Survival in Resected Node-Negative Small Bowel Adenocarcinoma: a SEER Database Analysis.

Small bowel adenocarcinoma (SBA) is a rare disease. Current recommendations are largely extrapolated from the colorectal literature. For node-negative (N -ve) cases, optimally stratifying cases into high or low risk, may help define optimal management. The objective of this analysis was to determine the importance of lymph node sampling for prognostication and to define what number of lymph nodes sampled is adequate. Cases of non-metastatic SBA with complete staging, pathologic, and demographic information were selected from the SEER database and SAS 9.4 software was used. Variables included age, gender, race, grade, TNM staging, and number of lymph nodes were examined. Comparisons were made between N -ve and N +ve cases. Survival analysis using N -ve cases was performed to characterize the impact of nodal sampling on survival and to determine which nodal cut-offs best predict survival. A total of 523 cases from 2004 to 2014 were included in this analysis. Statistically significant differences identified included the median number of nodes sampled between the N -ve and N +ve groups, and the distribution of T stage and grade. Survival analysis in the N -ve cases demonstrated that the strongest predictor of survival was sampling of 16 or more lymph nodes. In this analysis, lymph node sampling was shown to be the most important pathologic predictor of survival in cases of N -ve SBA. Replicating these findings in a secondary dataset and determining whether a clinical benefit of adjuvant chemotherapy exists for SBA patients with inadequate sampling are both important next steps.

Novel Prognostic Factors in Resected Small Bowel Adenocarcinoma

BackgroundSmall bowel adenocarcinoma (SBA) is a rare malignancy affecting approximately 3000 patients per year in the United States, and there is limited evidence prognosticating patients with resected SBA. We aimed to evaluate prognostic factors and the role of adjuvant therapy in patients with resected SBA. Patients and MethodsTwo hundred forty-one patients who had resected stage I-III SBA were retrospectively identified at a single tertiary referral institution. Overall survival (OS) analysis was performed by the Kaplan-Meier method, and Wilcoxon tests were used for statistical comparisons. Cox proportional hazards were performed to identify significant variables by univariate and multivariate analysis. ResultsMedian OS for the entire group was 54.5 months (95% confidence interval [CI], 37.2-81.2 months), with 5- and 10-year OS of 48% and 35%. Median follow-up was 113.7 months (95% CI, 97.9-126.6 months). For patients with stage III disease who received adjuvant therapy, the median OS was 33.8 months (95% CI, 27.8-78.8) compared to 24.7 months (95% CI, 11.5-37.8) for patients with no adjuvant therapy (P < .01). Male sex, advanced T stage, advanced N stage, increased positive lymph node ratio, lymphocyte-to-monocyte ratio < 1.56, presence of residual disease, and earlier date of diagnosis predicted worse survival on univariate analysis. Age > 60 years, lymphocyte-to-monocyte ratio < 1.56, and advanced T stage were identified as independent negative predictors of OS for all patients by multivariate analysis. ConclusionAdvanced age, advanced T stage, and lymphocyte-to-monocyte ratio < 1.56 independently predicted survival in resected SBA. Adjuvant therapy is associated with improved survival in patients with resected stage III SBA.

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

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 &lt; 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) &gt; 4.0, with a Hazard Ratio (HR) 0.13 (95% CI 0.007-0.69, p = 0.01), presurgical neutrophil to lymphocyte ratio (NLR) &lt; 8.0, HR 0.39 (95% CI 0.17-0.96, p = 0.04), and tumor size &lt; 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.

Randomized phase III study of observation versus adjuvant capecitabine and oxaliplatin in curatively resected small bowel adenocarcinoma: A Japan Clinical Oncology Group study (JCOG1502C).

TPS539 Background: Small bowel adenocarcinoma (SBA) is extremely rare tumor. Surgery is broadly applied as a standard treatment for localized SBA. However, the patients with localized SBA have poor prognosis even after curative resection (5-year survival: 40-65%), and most of them experience relapse. To prevent relapse, postoperative therapies are considered as most promising. However, there is no prospective study of postoperative therapies for curatively resected SBA patients and which regimens improve prognoses is unknown. For metastatic SBA, fluoropyrimidine and oxaliplatin is now regarded as global standard chemotherapy. Therefore, Japan Clinical Oncology Group (JCOG) planned a multicenter randomized phase III trial to confirm the superiority of postoperative capecitabine and oxaliplatin (CAPOX) to observation for curatively resected SBA under the Advanced Medical Care System of the Ministry of Health, Labour and Welfare, Japan. This study is a counterpart trial of BALLAD trial conducted in International Rare Cancer Initiative (IRCI) (clinical trials gov; NCT02502370), and the integrated analysis of BALLAD trial and JCOG1502C is planned. Methods: Eligibility criteria include histologically proven adenocarcinoma located in the duodenum (except Ampulla of Vater) / jejunum / ileum, curatively resected with regional lymph nodes dissection, pathological stage I (T1b-2N0M0) / stage II / stage III. Eligible patients are randomized into observation arm or CAPOX arm. CAPOX (130 mg/m2 of oxaliplatin on day 1, and 1000 mg/m2 of capecitabine twice a day for 14 days) is repeated every 3 weeks for 6 months (total 8 courses). The primary endpoint is RFS. The 3-year RFS of observation arm is assumed to be 70% and expected a 10% increase in CAPOX arm. The sample size was calculated as 150 (75 per arm) with a one-sided alpha level of 10%, a statistical power of 70%, an accrual period of 6.5 years. This study has been registered in the UMIN Clinical Trials Registry (UMIN000027280). This trial was activated in 9 May 2017, and no patients was enrolled as of Sep 2017. We will increase the number of participating sites up to 20 throughout Japan. Clinical trial information: UMIN000027280.

Duodenal localization is a negative predictor of survival after small bowel adenocarcinoma resection: A population-based, propensity score-matched analysis.

This study assessed the influence of tumor localization of small bowel adenocarcinoma on survival after surgical resection. Patients with resected small bowel adenocarcinoma, ACJJ stage I-III, were identified from the Surveillance, Epidemiology, and End Results database from 2004 to 2013. The impact of tumor localization on overall and cancer-specific survival was assessed using Cox proportional hazard regression models with and without risk-adjustment and propensity score methods. Adenocarcinoma was localized to the duodenum in 549 of 1025 patients (53.6%). There was no time trend for duodenal localization (P = 0.514). The 5-year cancer-specific survival rate was 48.2% (95%CI: 43.3-53.7%) for patients with duodenal carcinoma and 66.6% (95%CI: 61.6-72.1%) for patients with cancer located in the jejunum or ileum. Duodenal localization was associated with worse overall and cancer-specific survival in univariable (HR = 1.73; HR = 1.81, respectively; both P < 0.001), multivariable (HR = 1.52; HR = 1.65; both P < 0.001), and propensity score-adjusted analyses (HR = 1.33, P = 0.012; HR = 1.50, P = 0.002). Furthermore, young age, retrieval of more than 12 regional lymph nodes, less advanced stage, and married matrimonial status were positive, independent prognostic factors. Duodenal localization is an independent risk factor for poor survival after resection of adenocarcinoma.

Clinical outcomes of resectable small bowel adenocarcinoma treated by surgery alone: Case series in a Japanese single institution.

372 Background: Small bowel adenocarcinoma (SBA) is known as a poor prognostic cancer even in surgically resected cases. Its five-year survival rates were reported as 65%, 48%, and 35% in stage I, II, and III SBA, respectively. However, clinical outcomes of curatively resected SBA, especially without peri-operative adjuvant chemotherapy, are still unknown in Japanese population. Methods: We retrospectively reviewed medical records of patients who were diagnosed as Stage I, II, and III SBA after curative surgery between July 1994 and June 2014 at National Cancer Center Hospital. Overall survival (OS) and relapse-free survival (RFS) were calculated by Kaplan-Meier method. Cox proportional-hazards analysis was performed to identify the prognostic factors. Results: From a total of 76 patients with SBA received surgical resection, 56 were selected in this study who underwent curative resection with histological confirmation and did not receive adjuvant chemotherapy. The median age was 64 years (range: 20-85). Thirty-five patients (61%) were male. Forty-five patients (80%) had tumors in duodenum, 6 (11%) in jejunum and 5 (9%) in ileum. Pathological T stage were pT1a/T1b/T2/T3/T4 in 9/2/4/14/27 patients, and pathological N stage (pN) were pN0/N1/N2 in 29/16/11. The 1/3/5-year OS in all patients were 92.5/77.5/71.6%, and 1/3/5-year RFS were 76.5/68.9/61.6%. The 5-year RFS of pN0 (stage I/IIA/IIB) / N1 (stage IIIA) /N2 (stage IIIB) were 81.2/51.6/20.8%, and 5-year OS were 88.2/71.6/26.7%, respectively. Univariate analysis demonstrated that pN, presence of lymphatic and venous invasion were associated with poor OS. In multivariate analysis, pN was a significant predictor of poor OS (HR: 5.39 [N0 vs N1], 21.74 [N0 vs N2], 4.03 [N1 vs N2], p = 0.042). These findings were also seen in RFS. Conclusions: This study showed survival outcome of curatively resected SBA was better compared with previous reports, and pN was a significant prognostic factor of RFS and OS.

Efficacy of adjuvant chemotherapy for small bowel adenocarcinoma: A propensity score-matched analysis.

The role of adjuvant chemotherapy (AC) in the treatment of small bowel adenocarcinoma is poorly defined. Previous analyses have been limited by small sample sizes and have failed to demonstrate a survival advantage. Patients with resected small bowel adenocarcinoma (American Joint Committee on Cancer [AJCC] pathologic stage I-III) who were receiving AC (n = 1674) or surgery alone (SA; n = 3072) were identified in the NCDB (1998-2011). Cox regression identified covariates associated with overall survival (OS). AC and SA cohorts were matched (1:1) by propensity scores based on the likelihood of receiving AC or the survival hazard from Cox modeling. OS was compared with Kaplan-Meier estimates. The omission of AC conferred an increased risk of death (hazard ratio, 1.36; 95% confidence interval, 1.24-1.50; P < .001). After propensity score matching, there was a nonsignificant trend toward improved OS with AC in AJCC stage I patients (158.8 vs 110.7 months; P = .226) and AJCC stage II patients (104.0 vs 79.6 months; P = .185), including the subset with a T4 tumor classification (64.0 vs 47.4 months; P = .130) or a positive resection margin (44.4 vs 31.0 months; P = .333). Median OS was superior for patients with AJCC stage III disease who were receiving AC versus SA (42.4 vs 26.1 months; P < .001). These data support the use of AC for resected stage III small bowel adenocarcinoma. The trend toward improved OS for patients without nodal metastasis, including those who have T4 tumors or have undergone positive-margin resection, may justify the use of AC in select patients with earlier stage disease. Cancer 2016;122:693-701. © 2015 American Cancer Society.

Rare but Real: Management of Small Bowel Adenocarcinoma

Despite representing the longest segment of the alimentary tract, small bowel adenocarcinomas are rare. The diagnosis of small bowel adenocarcinoma is frequently delayed because of the nonspecific clinical symptoms and the limitations of small bowel imaging. The majority of patients will present with either lymph node or distant metastatic disease. Though the role of adjuvant therapy for resected small bowel adenocarcinoma is unclear, recent research efforts have led to an improvement in our management of advanced disease. Prospective phase II studies have successfully enrolled patients with this rare tumor type and have established the combination of a fluoropyrimidine and oxaliplatin as the most appropriate front-line chemotherapy for patients with advanced disease. Currently, five prospective clinical trials have been designed for patients with small bowel adenocarcinoma and enrollment to these clinical trials should be encouraged.

Rare but Real: Management of Small Bowel Adenocarcinoma

Despite representing the longest segment of the alimentary tract, small bowel adenocarcinomas are rare. The diagnosis of small bowel adenocarcinoma is frequently delayed because of the nonspecific clinical symptoms and the limitations of small bowel imaging. The majority of patients will present with either lymph node or distant metastatic disease. Though the role of adjuvant therapy for resected small bowel adenocarcinoma is unclear, recent research efforts have led to an improvement in our management of advanced disease. Prospective phase II studies have successfully enrolled patients with this rare tumor type and have established the combination of a fluoropyrimidine and oxaliplatin as the most appropriate front-line chemotherapy for patients with advanced disease. Currently, five prospective clinical trials have been designed for patients with small bowel adenocarcinoma and enrollment to these clinical trials should be encouraged.

Is there a role for adjuvant therapy in resected adenocarcinoma of the small intestine

Background. The benefit of adjuvant therapy for resected small bowel adenocarcinoma has not been proven. We undertook a retrospective analysis to evaluate the benefit of adjuvant therapy in a clearly defined patient population with curatively resected small bowel adenocarcinoma. Material and methods. We identified 54 patients with small bowel adenocarcinoma who underwent margin-negative surgical resection and were evaluated after surgery at the University of Texas, M. D. Anderson Cancer Center between 1990 and 2008. Disease-free survival (DFS) and overall survival (OS) were estimated. Results. Median age was 55 years and primary tumor site was duodenum in 67%, jejunum in 20%, and ileum in 13%. Thirty patients (56%) received adjuvant therapy consisting of systemic chemotherapy with or without radiation in 28 and radiation alone in two. Patients who received adjuvant therapy had significantly higher tumor stage and rate of lymph node involvement. Five-year DFS and OS did not differ between treatment groups. In multivariate analysis, the use of adjuvant therapy was associated with improved DFS (HR 0.27; 95% CI 0.07–0.98, P = 0.05) but not OS (HR 0.47; 95% CI 0.13–1.62, P = 0.23). In patients with a high risk of relapse (defined as a lymph node ratio ≥10%), adjuvant therapy appeared to improve OS, P = 0.04, but not DFS, P = 0.15. Discussion. The use of adjuvant therapy for curatively resected small bowel adenocarcinoma was associated with an improvement in DFS. This finding strongly supports further investigation of adjuvant chemotherapy in this tumor type.